Revver Collection My Videos

RNA-polymerase-2

Thu, 03 Nov 2005 20:42:49 +0000

RNa polymerase 3D animation (scientific/education video)

RNA-polymerase-3

Thu, 03 Nov 2005 21:35:58 +0000

3D animation of RNA polymerase from bacteriophage

RNA polymerase-part 1

Sat, 05 Nov 2005 11:29:44 +0000

Biochemistry video- RNA polymerase;RNA polymerase in action. The structure includes a very small RNA polymerase that is made by the bacteriophage T7, shown here with blue tubes. A small transcription bubble, composed of two DNA strands and an RNA strand, is bound in the active site. Notice how the two DNA strands form a double helix at the top of the picture. The enzyme separates them in the middle and builds an RNA strand using the DNA on the right. Finally, at the bottom, the two DNA strands come back together.

Vitamin D receptor

Sat, 05 Nov 2005 11:56:11 +0000

Rotating animation of vitamin D receptor Vitamin D deficiency is known to cause several bone diseases, due to insufficient calcium in the bones:

Vitamin D

Wed, 06 Dec 2006 06:05:01 +0000

Vit D and its receptor in low resolution for smaller screens

Vitamin D receptor -1

Wed, 06 Dec 2006 06:26:17 +0000

itamin D refers to a group of fat-soluble prohormones as well as to the metabolites and analogues of these substances. Two major forms of vitamin D are D2 (or ergocalciferol) and D3 or cholecalciferol.[1] Vitamin D3 is produced in skin exposed to sunlight, specifically ultraviolet B radiation. Very few foods are naturally rich in vitamin D, and most vitamin D intake is in the form of fortified products including milk and cereal grains.[1] Vitamin D plays an important role in the maintenance of several organ systems.[2] * Vitamin D regulates the calcium and phosphorus levels in the blood by promoting their absorption from food in the intestines, and by promoting re-absorption of calcium in the kidneys. * Vitamin D promotes bone formation and mineralization and is essential in the development of an intact and strong skeleton. * Vitamin D inhibits parathyroid hormone secretion from the parathyroid gland. * Vitamin D affects the immune system by promoting immunosuppression and anti-tumor activity. Vitamin D deficiency can result from; inadequate intake coupled with inadequate sunlight exposure, disorders that limit its absorption, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders, or, rarely, by a number of hereditary disorders.[2] Deficiency results in impaired bone mineralization, and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis.[2] ergosterol, lamisterol, made, from, dehydrositosterol, dihydrovitamin, biochemistry, science, cholecalciferol, vitamin, dihydrotachysterol, forms, dehydrocholesterol, ergocalciferol

Vitamin D (2)

Wed, 06 Dec 2006 06:26:17 +0000

ergosterol, lamisterol, made, from, dehydrositosterol, dihydrovitamin, biochemistry, science, cholecalciferol, vitamin, dihydrotachysterol, forms, dehydrocholesterol, ergocalciferol itamin D refers to a group of fat-soluble prohormones as well as to the metabolites and analogues of these substances. Two major forms of vitamin D are D2 (or ergocalciferol) and D3 or cholecalciferol.[1] Vitamin D3 is produced in skin exposed to sunlight, specifically ultraviolet B radiation. Very few foods are naturally rich in vitamin D, and most vitamin D intake is in the form of fortified products including milk and cereal grains.[1] Vitamin D plays an important role in the maintenance of several organ systems.[2] * Vitamin D regulates the calcium and phosphorus levels in the blood by promoting their absorption from food in the intestines, and by promoting re-absorption of calcium in the kidneys. * Vitamin D promotes bone formation and mineralization and is essential in the development of an intact and strong skeleton. * Vitamin D inhibits parathyroid hormone secretion from the parathyroid gland. * Vitamin D affects the immune system by promoting immunosuppression and anti-tumor activity. Vitamin D deficiency can result from; inadequate intake coupled with inadequate sunlight exposure, disorders that limit its absorption, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders, or, rarely, by a number of hereditary disorders.[2] Deficiency results in impaired bone mineralization, and leads to bone softening diseases, rickets in children and osteomalacia in adults, and possibly contributes to osteoporosis.[2] Contents [hide] * 1 Forms * 2 Biochemistry o 2.1 Synthesis mechanism (form 3) o 2.2 Mechanism of action * 3 Nutrition o 3.1 In food * 4 Diseases caused by deficiency o 4.1 Groups with greater deficiency risk * 5 Overdose * 6 Role in immunoregulation * 7 Role in cancer prevention and recovery * 8 Notes and references * 9 External links

Vitamin D receptor (3)

Wed, 06 Dec 2006 06:26:17 +0000

[edit] Diseases caused by deficiency The isolation of vitamin D and its functional role in rickets was determined by Edward Mellanby between 1918–1920. The 1928 Nobel Prize was awarded to Adolf Windaus, who discovered the steroid, 7-dehydrocholesterol, the precursor of vitamin D. Vitamin D deficiency is known to cause several bone diseases[11] including: * Rickets, a childhood disease characterized by impeded growth, and deformity, of the long bones. * Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterised by proximal muscle weakness and bone fragility. * Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility. Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases such as tuberculosis, cancer, chronic pain, several autoimmune diseases, high blood pressure, depression, and seasonal affective disorder.[8] [edit] Groups with greater deficiency risk Vitamin D requirements increase with age and the ability of skin to convert 7-dehydrocholesterol to pre-vitamin D3 decreases. In addition the ability of the kidneys to convert calcidiol to its active form, also decreases with age, prompting the need for increased vitamin D supplementation, in elderly individuals. The Canadian and American Pediatric Associations advise vitamin D supplementation from birth onwards, with 200 IU/day (5 mcg/d) in the south up to 800 IU/day in the north.[1] . While infant formula is generally fortified with vitamin D, breast milk does not contain significant levels of vitamin D, and parents are usually advised to avoid exposing babies to prolonged exposure to sunlight. Therefore, infants who are exclusively breastfed require vitamin D supplements. Liquid "drops" of vitamin D, as a single nutrient or combined with other vitamins, are available in water based or oil-based preparations ("Baby Drops" in North America, or "Vigantol oil" in Europe). Obese individuals may have lower levels of the circulating form of vitamin D, probably due to reduced bioavailability, and are at higher risk of deficiency. Patients with chronic liver disease or intestinal malabsorption may require larger doses of vitamin D (up to 40,000 IU or 1 mg (1000 micrograms) daily). To maintain blood levels of calcium, therapeutic vitamin D doses are sometimes administered (up to 100,000 IU or 2.5 mg daily) to patients who have had their parathyroid glands removed (most commonly renal dialysis patients who have had tertiary hyperparathyroidism, but also patients with primary hyperparathyroidism) or who suffer with hypoparathyroidism.[12] Those who avoid or are not exposed to midday sunshine may also require vitamin D supplements. Although a few minutes of exposure for light-skinned individuals may be all that is required, the dermatology community contends that even a few minutes of unprotected ultraviolet exposure a day increases the risk of skin cancer and causes photoaging of the skin. The use of sunscreen with an sun protection factor (SPF) of 8 inhibits more than 95% of vitamin D production in the skin.[8] To avoid vitamin D deficiency dermatologists recommend supplementation along with sunscreen use. Recent studies showed that, following the successful "Slip-Slop-Slap" health campaign encouraging Australians to cover up when exposed to sunlight to prevent skin cancer, an increased number of Australians and New Zealanders became vitamin D deficient.[13] Ironically, there are indications that vitamin D deficiency may lead to skin cancer.[14] At higher latitudes (above 30°), the decreased angle of the sun's rays, reduced daylight

vitamin D (4)

Wed, 06 Dec 2006 07:02:01 +0000

At higher latitudes, total vitamin D input from sunlight is usually insufficient, especially in the winter. To minimize risk of low vitamin D concentrations, foods such as milk are often fortified with vitamin D2 and/or vitamin D3, typically providing 100 IU per glass.[1] Fortified foods are the major dietary sources of vitamin D. Prior to the fortification of milk products with vitamin D rickets, was a major public health problem. Since the 1930s, milk has been fortified with 10 micrograms (400 IU) of vitamin D per quart, in the United States, where rickets is now uncommon.[8] One cup of vitamin D fortified milk supplies about one-fourth of the official estimated adequate intake of vitamin for adults older than age 50 years. Although milk is often fortified with vitamin D, dairy products made from milk (cheese, yogurt, ice cream, and so forth) are generally not. Only a few foods naturally contain significant amounts of vitamin D, including:[1] * Fish liver oils, such as cod liver oil, 1 Tbs. (15 mL), 1,360 IU * Fatty fish, such as: o Salmon, cooked, 3.5 oz, 360 IU o Mackerel, cooked, 3.5 oz, 345 IU o Sardines, canned in oil, drained, 1.75 oz, 250 IU o Tuna, canned in oil, 3 oz, 200 IU o Eel, cooked, 3.5 oz, 200 IU * One whole egg, 20 IU * Shiitake mushrooms, one of a few natural sources of vegan and kosher vitamin D (in the form of ergosterol vitamin D2) The U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) of vitamin D for childern and adults is 50 micrograms/day (2000 IU/day). For infants (birth to 12 months) the UL is 25 micrograms/day (1000 IU/day).

Vitamn D chapter 5

Wed, 06 Dec 2006 07:02:01 +0000

Vitamin D lesson 6

Wed, 06 Dec 2006 07:02:01 +0000

The isolation of vitamin D and its functional role in rickets was determined by Edward Mellanby between 1918–1920. The 1928 Nobel Prize was awarded to Adolf Windaus, who discovered the steroid, 7-dehydrocholesterol, the precursor of vitamin D. Vitamin D deficiency is known to cause several bone diseases[11] including: * Rickets, a childhood disease characterized by impeded growth, and deformity, of the long bones. * Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterised by proximal muscle weakness and bone fragility. * Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility. Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases such as tuberculosis, cancer, chronic pain, several autoimmune diseases, high blood pressure, depression, and seasonal affective disorder.[8] [edit] Groups with greater deficiency risk At higher latitudes (above 30°), the decreased angle of the sun's rays, reduced daylight hours in winter, and protective clothing worn to guard against cold weather, diminish absorption of sunlight and the production of vitamin D. Because melanin acts like a sun-block, prolonging the time required to generate vitamin D, dark-skinned individuals, in particular, may require extra vitamin D to avoid deficiency. At latitudes below 30° where sunlight and day-length are more consistent, and vitamin D supplementation may not be required.[15] The

Vitamin D 7

Wed, 06 Dec 2006 07:02:01 +0000

Vitamin D requirements increase with age and the ability of skin to convert 7-dehydrocholesterol to pre-vitamin D3 decreases. In addition the ability of the kidneys to convert calcidiol to its active form, also decreases with age, prompting the need for increased vitamin D supplementation, in elderly individuals. The Canadian and American Pediatric Associations advise vitamin D supplementation from birth onwards, with 200 IU/day (5 mcg/d) in the south up to 800 IU/day in the north.[1] . While infant formula is generally fortified with vitamin D, breast milk does not contain significant levels of vitamin D, and parents are usually advised to avoid exposing babies to prolonged exposure to sunlight. Therefore, infants who are exclusively breastfed require vitamin D supplements. Liquid "drops" of vitamin D, as a single nutrient or combined with other vitamins, are available in water based or oil-based preparations ("Baby Drops" in North America, or "Vigantol oil" in Europe). Obese individuals may have lower levels of the circulating form of vitamin D, probably due to reduced bioavailability, and are at higher risk of deficiency. Patients with chronic liver disease or intestinal malabsorption may require larger doses of vitamin D (up to 40,000 IU or 1 mg (1000 micrograms) daily). To maintain blood levels of calcium, therapeutic vitamin D doses are sometimes administered (up to 100,000 IU or 2.5 mg daily) to patients who have had their parathyroid glands removed (most commonly renal dialysis patients who have had tertiary hyperparathyroidism, but also patients with primary hyperparathyroidism) or who suffer with hypoparathyroidism.[12] Those who avoid or are not exposed to midday sunshine may also require vitamin D supplements. Although a few minutes of exposure for light-skinned individuals may be all that is required, the dermatology community contends that even a few minutes of unprotected ultraviolet exposure a day increases the risk of skin cancer and causes photoaging of the skin. The use of sunscreen with an sun protection factor (SPF) of 8 inhibits more than 95% of vitamin D production in the skin.[8] To avoid vitamin D deficiency dermatologists recommend supplementation along with sunscreen use. Recent studies showed that, following the successful "Slip-Slop-Slap" health campaign encouraging Australians to cover up when exposed to sunlight to prevent skin cancer, an increased number of Australians and New Zealanders became vitamin D deficient.[13] Ironically, there are indications that vitamin D deficiency may lead to skin cancer.[14]

Cytochrome p450 - part 1

Wed, 13 Dec 2006 06:19:11 +0000

If you have a headache and take a drug to block the pain, you'll notice that the effects of the drug wear off in a few hours. This happens because you have a powerful detoxification system that finds unusual chemicals, like drugs, and flushes them out of your body. This system fights all sorts of unpleasant chemicals that we eat and breathe, including drugs, poisonous compounds in plants, carcinogens formed during cooking, and environmental pollutants. The cytochrome p450 enzymes are our first line of defense in this chemical battle

The Drug Detox Factory

Wed, 13 Dec 2006 06:40:30 +0000

The cytochrome p450 enzymes find unusual molecules and add oxygen atoms to them. In most cases, this has the effect of making the molecule more soluble in water, and thus, easier to flush out of the body. The added oxygen also provides a ready handle for other detoxifying enzymes to take hold and further modify, and destroy, these toxic molecules. This task of adding oxygen is chemically tricky, and cytochrome p450 enzymes use a powerful molecular tool to perform the reaction: an iron atom in a heme group (described in more detail later). p450 Everywhere Cytochrome p450 enzymes are found in all organisms. Each organism builds several different enzymes, each of which act on a different selection of molecules. Typical bacteria have about 20 different forms and we make about 60. Plants often make hundreds of different forms. This is because plants make unusual pigments and exotic toxins to protect themselves. Many of the reactions needed to make these molecules are performed by specialized cytochrome p450 enzymes. For more information on cytochrome p450 from a genomics persective, take a look at the Protein of the Month at the European Bioinformatics Institute

Valium Detoxification

Wed, 13 Dec 2006 06:55:12 +0000

The molecule shown here is CYP3A4 (the cytochrome p450 that plays the major role in drug detoxification in your body. It has been estimated that this enzyme acts on about half of known drugs. For instance, it modifies the antibiotic erythromycin, shown at the bottom in blue. It also detoxifies such diverse drugs as codeine, diazepam (Valium), paclitaxel (Taxol), and several anti-HIV drugs. In some cases, however, the reaction performed by cytochrome p450 enzymes can cause more harm than good. For example, CYP3A4 is partially responsible for the toxicity of large doses of acetaminophen (Tylenol). The modified form of acetaminophen is dangerously reactive, but it is normally cleared away quickly by other detoxifying enzymes. But with large doses, the reactive intermediate can build up to dangerous levels. Prescriptions and p450 Doctors must be careful to keep the cytochrome p450 enzymes in mind when they prescribe medications. For instance, you may have seen warnings on prescriptions, telling you not to drink grapefruit juice when taking a medication. Grapefruits contain a flavinol molecule that inhibits cytochrome p450 enzymes. This will slow down the detoxification of drugs, which may cause them to have stronger effects than expected by the doctor.

Cytochrome p450 -4

Fri, 15 Dec 2006 04:24:41 +0000

Cytochrome p450 enzymes also play a number of essential roles in the synthesis of normal cellular compounds. For instance, special cytochrome p450 enzymes are built to perform chemical steps in the construction of steroids, vitamins A and D, and lipid-like eicosanoid molecules involved in signaling. The enzyme shown here on the left is a fungal cytochrome p450 that performs a step in sterol synthesis (PDB entry 1ea1). A similar enzyme in our cells is needed for the synthesis of cholesterol. The enzyme complex on the right provides electrons for the reaction

The Factory of Life

Fri, 15 Dec 2006 05:09:41 +0000

The best-studied cytochrome p450 enzyme is a bacterial enzyme that adds oxygen to camphor. Two early structures are shown here. On the left (PDB entry 3cpp) is a structure with camphor and carbon monoxide bound in the active site. The carbon monoxide is an inhibitor that poisons the enzyme. It binds to the iron (large yellowish sphere in the middle of the heme) in the same place as oxygen gas. The cysteine amino acid at the bottom activates the iron. The structure on the right (PDB entry 1noo) shows camphor after the reaction, when an oxygen atom has been added (the other oxygen atom is released during the reaction as a water molecule). Looking through the PDB, you can find dozens of other structures of cytochrome p450cam, showing many different molecules bound in the small active site, and showing many different stages in the reaction. ---- Cytochrome P450 oxidase (abbreviated CYP or CYP450) is a generic term for a large number of evolutionary related oxidative enzymes (EC 1.14) important in animal, plant, and bacterial physiology. Most cytochromes P450 (CYPs) have about 525 amino acids and a heme (hæm) group at the active site. Most animal and plant CYPs have electron transfer protein cofactors, cytochrome P450 reductase and cytochrome b5, and use molecular oxygen (O2) to function, while bacterial CYPs use other protein cofactors to function. CYP homologs have been sequenced from all lineages of life, including mammals, birds, fish, insects, worms, sea squirts, sea urchins, plants, fungi, slime molds, bacteria and archaea. More than 6400 distinct CYP sequences are known and officially named (as of October 2006; see the web site of the P450 Nomenclature Committee for current counts).

Cytochrome p450 superfamily

Fri, 15 Dec 2006 18:33:32 +0000

The name P450 refers to the "pigment at 450 nm", so named for the characteristic Soret peak formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (with sodium dithionite) and complexed Animal CYPs are primarily membrane-associated proteins, located either in the inner membrane of mitochondria or in the endoplasmic reticulum of cells. CYPs metabolise thousands of endogenous and exogenous compounds. Most CYPs can metabolize multiple substrates, and many can catalyze multiple reactions, which accounts for their central importance in metabolizing the potentially endless variety of endogenous and exogenous molecules. In the liver, these substrates include drugs and toxic compounds as well as metabolic products such as bilirubin (a breakdown product of hemoglobin). Cytochromes P450 are present in many other tissues of the body including the mucosa of the gastrointestinal tract, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. In most animals, including humans, hepatic cytochromes P450 are the most widely studied of the P450 enzymes. The Human Genome Project has identified 63 human genes (57 full genes and 5 pseudogenes) coding for the various cytochrome P450 enzymes [1]. Drug Metabolism In drug metabolism, cytochrome P450 is probably the most important element of oxidative metabolism (also known as Phase I metabolism) in animals (metabolism in this context being the chemical modification or degradation of chemicals including drugs and endogenous compounds). Many drugs may increase or decrease the activity of various CYP isozymes in a phenomenon known as enzyme induction and inhibition). This is a major source of adverse drug interactions, since changes in CYP enzyme activity may affect the metabolism and clearance of various drugs. For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body to toxic levels, possibly causing an overdose. Hence, these drug interactions may necessitate dosage adjustments or choosing drugs which do not interact with the CYP system. In addition, naturally occurring compounds may also cause a similar effect. For example, bioactive compounds found in grapefruit juice and some other fruit juices, including bergamottin, dihydroxybergamottin, and paradisin-A, have been found to inhibit CYP3A4-mediated metabolism of certain medications, leading to increased bioavailability and thus the strong possibility of overdosing. Because of this risk, avoiding grapefruit juice and fresh grapefruits entirely while on drugs is usually advised. [edit] P450s in Plants Plant cytochrome P450s are involved in a wide range of biosynthetic reactions, leading to various fatty acid conjugates, plant hormones, defensive compounds, or medically important drugs. Terpenoids, which represent the largest class of characterized natural plant compounds, are often metabolic substrates for plant CYPs

Coughing and sneezing

Mon, 18 Dec 2006 12:10:09 +0000

Little RNA Viruses Viruses are biological hijackers. They attack a living cell and force it to make many new viruses, often destroying the cell in the process. Picornaviruses, or "little RNA viruses," are among the most simple viruses. They are composed of a modular protein shell, which seeks out and binds to a target cell surface, surrounding a short piece of RNA, which contains all of the information needed to co-opt the cell's machinery and direct the construction of new viruses. In spite of their simplicity, or perhaps because of it, the picornaviruses are also among the most important viruses for human health and welfare. Three familiar examples are shown here: poliovirus at the top (PDB entry 2plv), rhinovirus at the center (PDB entry 4rhv), and the virus that causes foot and mouth disease in livestock at the bottom (PDB entry 1bbt). Specialization Poliovirus and rhinovirus have specialized to attack primarily human beings, but they use two different approaches. Poliovirus, which is found in three similar forms, is designed to attack a given person only once. It makes its offspring and then is off to the next person. In most cases, poliovirus causes a simple flu-like disease as it attacks cells in the digestive system. This infection is rapidly cleared up by the immune system. But in about 1 in 100 cases, the virus spreads to the nerve cells that control muscle motion, causing paralysis--polio myelitis--as the nerve cells are infected. Rhinovirus, on the other hand, is found in many different forms that attack a given person many times during their life. Each time you get a cold, a different form of rhinovirus (or occasionally, a different type of virus) is attacking. Your body learns how to fight it off, but you are still susceptible to the next form. On average, a person will have a new cold once every two years, so most of us are quite familiar with the symptoms of rhinovirus infection in our nose and respiratory tract. Because they are so simple, picornaviruses can be very stable. Rhinovirus can last for days on your hands and still be infectious. And because the virus is shed from infected people all through the period with symptoms and even for days after, it spreads effectively through contact from person to person.

Running nose

Mon, 18 Dec 2006 15:10:07 +0000

Vaccines Antibodies are our major defense against these small, efficient viruses. Vaccines prime the immune system with antibodies, making it ready to fight an infection. In the case of poliovirus, there are two types of vaccines. One is a killed version of the virus, which is slowly killed with formaldehyde over the course of several days so that it is inactivated, but still keeps its proper shape. The second is a weakened, but still live, strain of the virus that has been artificially bred to stimulate the immune system without causing disease. The immune system responds by making antibodies to fight these weakened viruses, leaving it ready to fight the real thing when it comes along. The polio vaccines are one of the triumphs of modern medicine, but many people would say that the lack of a cure for the common cold is one of the great failings. The difficulty of creating a vaccine for the common cold lies in the diversity of rhinovirus. Over one hundred types of rhinovirus have been discovered as they strike people around the world, and new strains appear continually. Rhinovirus is a moving target that is not effectively combated with a single vaccine. Antiviral drugs, however, are a possible solution. Picornavirus Structure Many viruses, including the picornaviruses and bacteriophage phiX174 (discussed in an earlier Molecule of the Month), are icosahedral in shape. They are composed of 60 identical pieces that form a perfectly symmetrical shell, termed a capsid, around the viral genome. In the case of poliovirus and rhinovirus, the shell is composed of 60 copies of four different proteins (colored yellow, orange, red, and magenta on rhinovirus here, PDB entry 4rhv), for a total of 240 protein chains in all. Notice that the fourth chain, colored magenta, can only be seen on the inside surface of the capsid. These proteins are carefully designed to be stable, but not too stable. They must be fairly sturdy to allow the virus to pass from host to host through the hostile environment. But at the same time, they must be able to fall apart when they enter the cell, releasing the RNA inside. A carefully orchestrated set of structural changes occur as the virus attaches to the surface of the cell and is drawn inside, allowing the virus to deliver its RNA into the unwitting host.

Rhinovirus (part 3)

Mon, 18 Dec 2006 16:49:07 +0000

The RNA protected inside the capsid is seen only as a blurry tangle in these crystallographic structures and is not shown in these pictures, because it is not as perfectly symmetrical as the many proteins in the shell. The rhinovirus genome, when analyzed by sequencing techniques, contains just enough information to direct the construction of eleven proteins. These include the four separate proteins for its capsid, another four proteins that replicate its RNA, two proteins to clip each of these proteins into the proper shape, and one additional protein with as- to deliver its RNA into the unwitting host. yet obscure function. Antibodies bind to the surface of picornaviruses and stop them from attacking cells. In the left picture, rhinovirus is bound to a receptor protein on the cell surface, shown in blue (from PDB entry 1dgi). Notice that the receptor protein is gripped within a groove that encircles the five-fold symmetrical arrangement of proteins shown in yellow (known as the canyon in the picornavirus literature). Antibodies bind to the surface of rhinovirus and poliovirus in this same position and block their attachment to the surfaces of cells. The right picture shows fragments of antibodies (in light blue) bound to rhinovirus (from PDB entry 1rvf). The intact antibodies are much larger than the small fragments seen here, so seven to ten antibodies are enough to form a bulky barrier on each virus to block attachment and infection. Many structures of rhinovirus with antiviral drugs are available at the PDB, including the drug pleconaril, currently in clinical testing, shown here (PDB entry 1c8m). In this illustration, the drug is shown in spheres, and only four protein chains are shown, instead of the entire capsid. The inside of the virus is towards the bottom of the figure and the deep groove where the cellular receptor and antibodies bind can be seen on the upper side, shown with an arrow. Most drugs act by blocking protein binding sites or destabilizing a key interaction. These drugs, on the other hand, may act differently. They actually stabilize the virus structure so that it cannot release its cargo of RNA. The drugs bind in a little pocket under the deep groove that grabs onto the cellular receptor. Normally, the binding of virus to receptor shifts the structure of the virus, ultimately allowing the virus to release RNA. The drug, however, glues the virus shut. Rhinovirus (from the Greek rhin-, which means "nose") is a genus of the Picornaviridae family of viruses. Rhinoviruses are the most common viral infective agents in humans, and a causative agent of the common cold. There are over 105 serologic virus types that cause cold symptoms, and rhinoviruses are responsible for approximately 50% of all cases.

Common Cold

Mon, 18 Dec 2006 13:49:09 +0000

Rhinoviruses have single-stranded positive sense RNA genomes of between 7.2 and 8.5kb in length. At the 5' end of the genome is a virus-encoded protein, and like mammalian mRNA, there is a 3' poly-A tail. Structural proteins are encoded in the 5' region of the genome and non structural at the end. This is the same for all picornaviruses. The viral particles themselves are not enveloped and are icosahedral in structure. Rhinoviruses are composed of a capsid, that contains four viral proteins VP1, VP2, VP3 and VP4.[1][2] VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure and lies at interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an icosahedron. Antibodies are a major defense against infection with the epitopes lying on the exterior regions of VP1-VP3. Transmission and epidemiology Rhinoviruses have two main modes of transmission: In the past it was obvious that these viruses were transmitted directly from person-to-person via aerosols of respiratory droplets. However, now they are known to be transmitted indirectly via respiratory droplets that are deposited on the hands and then transported by fingers to the nose or eyes. Rhinoviruses occur worldwide causing disease especially at schools for example which enhance transmission during fall and winter. They show symptoms such as fever, cough, and nasal congestion. The frequency of colds is high in childhood and decreases during adulthood most probably because of the possession of immunity.

Rhinovirus-5

Mon, 18 Dec 2006 13:49:09 +0000

Most people are infected with a rhinovirus. The common cold occurs only when the immune system is weakened. The most common reason for this is stress. The primary route of entry for rhinoviruses is the upper respiratory tract. Afterwards, the virus binds to ICAM-1 (intracellular adhesion molecule -1) receptors on respiratory epithelial cells. As the virus replicates and spreads, infected cells release distress signals known as chemokines and cytokines (which in turn activate inflammatory mediators). Rhinoviruses rarely cause lower respiratory tract disease probably because they grow poorly at 37°C. Novel antiviral drugs Interferon-alpha used intranasally was shown to be protective to rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding, and resistance was also developing toward the drug. Hence, all research put into this drug was ceased. Pleconaril, is a bioavailable antiviral drug that is taken orally for treating infections caused by picornaviruses.[3] This drug acts by binding to a hydrophobic pocket in VP1 and stabilizes the protein capsid to such an extent that the virus cannot release its RNA genome into the target cell. When tested in volunteers, during the clinical trials, this drug caused a significant decrease in mucus secretions and illness-associated symptoms. Pleconaril is not currently available for treatment of rhinoviral infections, as its efficacy in treating these infections is under further evaluation.

Cholera toxin animation 1

Sat, 23 Dec 2006 08:03:30 +0000

Bacteria pull no punches when they fight to protect themselves. Some bacteria build toxins so powerful that a single molecule can kill an entire cell. This is far more effective than chemical poisons like cyanide or arsenic. Chemical poisons attack important molecules one by one, so many, many molecules of cyanide are needed to kill a cell. Bacterial toxins use two strategies to make their toxins far more deadly than this. Building a Deadly Toxin The first strategy used to build super-deadly toxins is to use a targeting mechanism to deliver the toxin directly to the unlucky cell. Cholera toxin, shown here from PDB entry 1xtc, has a ring of five identical protein chains, colored blue here, which binds to carbohydrates on the surface of cells. This delivers the toxic part of the molecule, colored red, to the cell, where it can wreak its havoc. The second deadly strategy is to use a toxic enzyme instead of a chemical poison. Enzymes are designed to perform their reactions over and over again, hopping from target to target and making their chemical changes. Thus, one enzyme can modify a whole cell full of molecules. Cholera uses this strategy once it gets inside cells. The toxic portion hops from molecule to molecule, disabling each one in turn, until the entire cell is killed. Cholera Toxin in Action The catalytic portion of cholera toxin performs a single function: it seeks out the G proteins used for cellular signaling and attaches an ADP molecule to them (for more on G-proteins, see the Molecule of the Month for March 2004 ). This converts the G-protein into a permanently active state, so it sends a never-ending signal. This confuses the cell, and among other things, it begins to transport lots of water and sodium outwards. This floods the intestine, leading to life-threatening dehydration.

Cholera toxin science video 2

Tue, 26 Dec 2006 19:02:38 +0000

Cholera Toxin in Action The catalytic portion of cholera toxin performs a single function: it seeks out the G proteins used for cellular signaling and attaches an ADP molecule to them (for more on G-proteins, see the Molecule of the Month for March 2004 ). This converts the G-protein into a permanently active state, so it sends a never-ending signal. This confuses the cell, and among other things, it begins to transport lots of water and sodium outwards. This floods the intestine, leading to life-threatening dehydration. The two-part strategy employed by cholera toxin is highly effective, so much so that it is used by many different organisms that seek to protect themselves. A few examples from the PDB are shown here, with the targeting portion in blue and the toxic enzyme in red. These include E. coli enterotoxin (PDB entry 1ltb), which looks and acts like cholera toxin and is a cause of intestinal problems when traveling. Pertussis toxin (PDB entry 1prt), made by the bacterium that causes whooping cough, also attacks the G-protein signaling pathway. Diphtheria toxin (PDB entry 1mdt) is synthesized as a single chain, but is then cut to form the two-part toxin when it is released. It shuts down protein synthesis in cells by attacking one of the elongation factors. Ricin (PDB entry 2aai) is a powerful toxin made by the castor bean plant. Once it gets inside cells, it blocks protein synthesis by directly attacking ribosomes. For more information on toxins from a genomics perspective, take a look at the Protein of the Month at the European Bioinformatics Institute.

Hemoglobin science video 1

Thu, 28 Dec 2006 18:18:27 +0000

Hemoglobin is the protein that makes blood red. It is composed of four protein chains, two alpha chains and two beta chains, each with a ring-like heme group containing an iron atom. Oxygen binds reversibly to these iron atoms and is transported through blood. Each of the protein chains is similar in structure to myoglobin (presented in the January 2000 Molecule of the Month), the protein used to store oxygen in muscles and other tissues. However, the four chains of hemoglobin give it some extra advantages, as described on the next page. Use and Abuse of Hemoglobin Aside from oxygen transport, hemoglobin can bind and transport other molecules like nitric oxide and carbon monoxide. Nitric oxide affects the walls of blood vessels, causing them to relax. This in turn reduces the blood pressure. Recent studies have shown that nitric oxide can bind to specific cysteine residues in hemoglobin and also to the irons in the heme groups, as shown in PDB entry 1buw. Thus, hemoglobin contributes to the regulation of blood pressure by distributing nitric oxide through blood. Carbon monoxide, on the other hand, is a toxic gas.

Biochemistry: HEMOGLOBIN

Fri, 29 Dec 2006 14:45:19 +0000

Red Blood, Blue Blood Ever wondered why blood vessels appear blue? Oxygenated blood is bright red: when you are cut, the blood you see is brilliant red oxygenated blood. Deoxygenated blood is deep purple: when you donate blood or give a blood sample at the doctor's office, it is drawn into a storage tube away from oxygen, so you can see this dark purple color. However, deep purple deoxygenated blood appears blue as it flows through our veins, especially in people with fair skin. This is due to the way that different colors of light travel through skin: blue light is reflected in the surface layers of the skin, whereas red light penetrates more deeply. The dark blood in the vein absorbs most of this red light (as well as any blue light that makes it in that far), so what we see is the blue light that is reflected at the skin's surface. Some organisms like snails and crabs, on the other hand, use copper to transport oxygen, so they truly have blue blood. Artificial Blood Blood transfusions have saved countless lives. However, the need for matching blood type, the short life of stored blood, and the possibility of contamination are still major concerns. An understanding of how hemoglobin works, based on decades of biochemical study and many crystallographic structures, has prompted a search for blood substitutes and artificial blood. The most obvious approach is to use a solution of pure hemoglobin to replace lost blood. The main challenge is keeping the four protein chains of hemoglobin together. In the absence of the protective casing of the red blood cell, the four chains rapidly fall apart. To avoid this problem, novel hemoglobin molecules have been designed where two of the four chains are physically linked together, as shown in PDB entry 1c7d. In that structure, two additional glycine residues form a link between two of the chains, preventing their separation in solution. Hemoglobin Cousins Looking through the PDB, you will find many different hemoglobin molecules. You can find Max Perutz's groundbreaking structure of horse hemoglobin in entry 2dhb, shown in the picture here. There are structures of human hemoglobins, both adult and fetal. You can also find unusual hemoglobins like leghemoglobin, which is found in legumes. It is thought to protect the oxygen-sensitive bacteria that fix nitrogen in leguminous plant roots. In the past few years some hemoglobin cousins called the "truncated hemoglobins" have been identified, such as the hemoglobin in PDB entry 1idr, which have several portions of the classic structure edited out. The only feature that is absolutely conserved in this subfamily of proteins is the histidine amino acid that binds to the heme iron.

Red Blood Cells (EPO)

Tue, 02 Jan 2007 05:00:04 +0000

Cooperation Makes It Easier Hemoglobin is a remarkable molecular machine that uses motion and small structural changes to regulate its action. Oxygen binding at the four heme sites in hemoglobin does not happen simultaneously. Once the first heme binds oxygen, it introduces small changes in the structure of the corresponding protein chain. These changes nudge the neighboring chains into a different shape, making them bind oxygen more easily. Thus, it is difficult to add the first oxygen molecule, but binding the second, third and fourth oxygen molecules gets progressively easier and easier. This provides a great advantage in hemoglobin function. When blood is in the lungs, where oxygen is plentiful, oxygen easily binds to the first subunit and then quickly fills up the remaining ones. Then, as blood circulates through the body, the oxygen level drops while that of carbon dioxide increases. In this environment, hemoglobin releases its bound oxygen. As soon as the first oxygen molecule drops off, the protein starts changing its shape. This prompts the remaining three oxygens to be quickly released. In this way, hemoglobin picks up the largest possible load of oxygen in the lungs, and delivers all of it where and when needed. In this animated figure, the heme group of one subunit, shown in the little circular window, is kept in one place so that you can see how the protein moves around it when oxygen binds. The oxygen molecule is shown in blue green. As it binds to the iron atom in the center of the heme, it pulls a histidine amino acid upwards on the bottom side of the heme. This shifts the position of an entire alpha helix, shown here in orange below the heme. This motion is propagated throughout the protein chain and on to the other chains, ultimately causing the large rocking motion of the two subunits shown in blue. The two structures shown are PDB entries 2hhb and 1hho.