Canine Cauliflower Ear

ARSENIC AND DNA supercoiling. CARNIVAL OF THE

Cleaning Brown Marks On Stainless Steel

BIODIVERSITY '

Period Burn When Urinate

Fever

When the cold became slightly more pungent, like every year, I made an annoying cold. Apart from that everything runs as usual, there are the usual family quarrels and unnecessary school is pretty good. It is a time that I feel a bit 'lost , a bit' lost in all my conflicting thoughts and I would need even more cuddles and affection. I happen to think about the past and experience a 'distress devastating, but if I think about the future I can not imagine anything. Dark, full vacuum . I hope that my paranoia is exaggerated quest'accentuazione only due to fever and to pass soon.

{ And I find it kind of funny, I find it kind of sad The Dreams In Which I'm dying are the best I've ever had. I find it hard to tell you, I find it hard to take When people run in circles it's a very very mad world / / Mad World - Gary Jules ♪ }

French Country Farmhouse Decorating

Neuraminidase

var _gaq _gaq = : 'Http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName ('script') [0]; s.parentNode.insertBefore (ga, s);} ) ();
The flu virus is constantly evolving, every year we hear of new strains, in fact, every decade or so, a new strain is dangerous and poses a threat to public health. Last year, there was an outbreak of a new strain of flu virus, the '
H1N1, more commonly known as swine flu virus. The name H1N1 refers to two types of molecules that coat the surface of the virus: hemagglutinin
and neuraminidase . Together, these two molecules determines the infectivity of the virus. The hemagglutinin plays a decisive role when the virus approaches the cell by binding to the polysaccharide chains on the cell surface and then injecting the
viral DNA into the cell. The neuraminidase, on the other hand, comes into play when the virus leaves the infected cells. Ensures that the virus does not remain bound to the surface polysaccharides of cutting their chains.

Cut sugars

The neuraminidase, shown above from the PDB file 1nn2, consists of four identical subunits arranged a square. It is normally linked to the virus surface protein with a long arm, not shown. The active sites are located in deep depressions of the surface above, bind to cellular polysaccharide chains and cut the sugar terminal. The surface of the neuraminidase has linked some of the chains of polysaccharides in the structure above, we see extend upwards and downwards, and are similar to the polysaccharide chains present on the surface proteins of our cells.

Pigs and people

As the hemagglutinin, neuraminidase, even if there are several sittotipi known as N1-N9. These subtypes are defined by their interaction with antibodies: all variants of the same subtype are neutralized by the same type of antibodies. These subtypes are one of the causes of the continued aggression of influenza. Some subtypes can infect people, infect other birds and others can attack the pigs or other mammals. When different viruses infect the same body, the various subtypes can be mixed and combined in different ways, giving rise to new random combinations that occasionally can be particularly dangerous or even fatal, thus leading to the formation of new strains

. fight the flu are two most effective drugs currently in use to fight the flu: zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs have been discovered using crystal structures taken from PDB files. By studying the binding of various molecules with the active site of neuraminidase, the researchers were able to design new drugs that mimic the natural substrates of the enzyme. These molecules bind strongly in the active site and block the action that is essential for the release of virus from the cell membrane. Here are shown two structures of these drugs. the middle, PDB file 3b7e, zanamivir is shown (blue) linked to the English influenza virus neuraminidase that caused a pandemic in 1918. Below, PDB file 2hu4, oseltamivir is shown (blue) linked to the avian influenza virus neuraminidase.

Antibodies and vaccines When we get sick of influence, our immune system produces antibodies to fight the virus.
An influenza vaccine can prepare your immune system for this protective action by putting it in contact with a weakened virus or harmless fragments of the virus. In this way the vaccine makes the immune system to produce the right antibodies before infection occurs itself. antibodies recognize proteins on the surface of the virus. antibodies most effective are those that attack the hemagglutinin and thus block the infection of new cells.
antibodies against neuraminidase, such as those shown here in blue, the image comes from the PDB file 1NCA can make it lighter than the flu, and they too help to fight the virus.

explore the structure
To design a drug that could cure people should pay close attention. drugs should be different from the natural substrate of the enzyme so that the enzyme can not catalyze the reaction to destroy them. the same time, the drugs must be very similar to the natural substrate of the enzyme to bind strongly to the active site to block it. It 'also important that medications are similar to natural substrates to avoid drug resistance. An example of this problem is illustrated in three figures below The first figure shows the neuraminidase bound sialic acid in its active site, PDB file
2bat
. This figure shows the normal interaction of the enzyme with a polysaccharide, its natural substrate. The second figure shows the link with oseltamivir, a drug used to combat influenza, 2hu4 PDB file. Note that this is similar but not identical sialic acid. E 'slightly larger forces and a glutamic acid (pink) to bend a little' to the histidine on him (also pink). The third figure shows a variant of the enzyme who developed drug resistance, 3cl0 PDB file. In this mutant enzyme, histidine has been replaced by a tyrosine (Tyr274 pink), being larger, glutamic acid leads down to the drug. Oseltamivir can still bind, but in a less strong due to interference with glutamic acid (pink) and thus can be ousted out of the polysaccharide, the natural substrate. The drug is therefore ineffective in combating the virus mutant. However, there is still enough space to bind sialic acid, and then the mutant enzyme still functions to perform its normal action release of the virus.

Sources:
PDB

Concord Vampiro Cleats

haemagglutinin


var _gaq _gaq = genome consists of single-stranded RNA mold. Virulence of influenza there are three main types, named A, B, C. The main difference lies in the proteins of the major capsid nucleocapside.Le caratteistiche conferitici are two proteins found in extensions known as the spike protein. One is called hemagglutinin, the other neuraminidase. The first is also the rincpale protein on the surface of the virus, is also the main site of AACC by antibodies. It is also the protein that shows increased genetic drift, and it is precisely the root cause of the continuing development of new strains, so every year we end up with new vaccines.


The influenza virus is a dangerous enemy. Normally the immune system fights viral infections by killing the virus for several days and causing the annoying symptoms of influenza. Each year, influenza vaccines activate the immune system to enable it to fight the most common flu viruses. About every twenty years, it appears that a new flu strain is much more virulent than those pitches, and then spread with great rapidity. This happened, for example, at the end of World War causing a pandemic (known as English), which has killed more than 20 million people, more than twice as many people who were death in war.


Hook the target and attack
The hemagglutinin is one of the factors that make the virus so effective. It 's a tip-shaped protein that extends out from the surface of the virus. In the active form shown here, 1ruz PDB file, the hemagglutinin consists of two different types of chains shown in blue and beige. The chains are blue the latching mechanism of the target, looking for particular sugar chains on the cell surface. When found, the hemagglutinin binds to, thus engaging the virus to the cell, then the chains beige begin the attack, as shown on the next page. The name

hemagglutinin refers to the ability of influenza virus to agglutinate red blood cells: the virus is covered with several hemagglutinin molecules that can bind many red blood cells, creating a lump so large as to be visible.



Subtypes hidden

The specificity and thus the hazard of each strain of influenza virus hemagglutinin depends on the particular type he has. They know more than a dozen subtypes of hemagglutinins. Three of these, called H1, H2 and H3 (H is the original English name of hemagglutinin), attacked the man because they are able to recognize specific sugars on the surface of some cells in our section respiratory infection that's why we started there when the flu. Other subtypes such as H5, attack glycoproteins found in the digestive system of birds. Most of these subtypes is not dangerous to humans and not even the threat of bird life and thus constitutes a kind of hidden reservoir of virus. A potential danger, however, may come from the exchange of genes between different strains.

The H5N1 bird flu virus that has come to the front pages during this period, which is decimating the bird population, but is not currently a real danger to humans because they do not have the right to hemagglutinin attack human cells. (The acronym refers to an N1 subtype of a second viral protein surface: neuraminidase that the virus uses to break away from the infected cell and spread the infection). However, there is the possibility that the virus could acquire a hemagglutinin-specific man, and then we can cause real problems. This might, for instance, by pigs. Indeed, the latter are susceptible to both avian viruses to humans that. In cases where a pig was infected simultaneously by both types of virus, they may exchange genes during infection. In this way you could create a new virus with the virulence of avian viruses and more with the ability to attack human cells.

lethal agent

The hemagglutinin shown here has been derived from the virus causing the pandemic that has killed so many people in 1918, the English. The DNA coding for this hemagglutinin was isolated from samples stored and the hemagglutinin was synthesized in the laboratory in accordance with such genetic information. We have obtained two crystal structures, the active form shown here (PDB file 1ruz), and a precursor of the hemagglutinin, not shown (PDB file 1rd8). The protein is attached to the viral membrane by a short filament protein that can not be seen in the crystal structure and that there is schematically represented by the segments beige below.

haemagglutinin in action

The hemagglutinin is a ruthless molecular machine that engages and kills the cells. This process is accomplished in multiple steps.

In the first, the three binding sites on the top of the protein bind to sugars of some cell membrane glycoproteins shown in green in the top left of the figure (PDB file 1hge).

In the second step, the virus enters the cell by endocytosis, ie, the host cell as an endosome, intussusception of the cell membrane, which tries to digest the virus, creating an acid environment. The virus, however, resisted this attack, even the acid environment necessary for him to trigger the mechanism of its counterattack to the cell. Thanks to its acid, hemagglutinin opens and folds up taking a completely different structure. Slices of orange and red are usually tucked inside the protein, but are worn out in acid as shown in the middle of the figure above (PDB file 1htm, 1ibn, 2vir). The red portion is called fusion peptide, has a great affinity for membranes, it is part of the cell membrane and it clips securely to the virus.

In the third step, as shown on the right side of the figure (fike 1qu1 PDB), the portions are wrapped up as orange yellow contract and that makes the protein and forces the two membranes to approach almost to toccasi with each other. Finally, the two membranes fuse and the viral RNA enters the cell beginning the process of infection.

antibodies (mol of the month Sept 2001, Feb 2005, March 2005) are our first line of defense against the influenza virus. The PDB file 1qfu shows how a hemagglutinin antibody attacks the lock so that it can no longer bind to the cell surface.

The structure includes the hemagglutinin, shown in blue and yellow, and three copies of the Fab antibody fragment (the three fragments magenta encase the haemagglutinin).

course viruses develop strategies to escape the attack of the antibodies and thus are born every year new strains still able to infect. One strategy is to change the arrangement of carbohydrates on the hemagglutinin surface. These carbohydrates are shown in green in Fig. If the virus adds a new carbohydrate at the point where the antibody is bound, in the future to prevent quell'anticorpo to bond and have made it ineffective.

Sources:

PDB