Catalyst mystery unlocked Aug 19, 2008
"What really fits is the electrostatic interaction between the enzyme active site to the substrate charges at the so-called transition state, where the bonds are halfway to being broken," Warshel said. If Warshel is correct, catalyst and substrate would be less like lock and key, and more like two magnets: As long the opposite poles could get close to each other, they would bind. (EurekAlert!)
Researchers Unveil Vital Key To Cancer Aug 8, 2008
We wanted to see what this protein looked like at the molecular level and, by revealing the active site lock , help design a new inhibitory key to physically block the ATP-binding site. His colleague Dr Lydia Tabernero added: This work presents the first crystallographic structure of human Mps1, an important regulator of chromosomal stability and a potential target in cancer therapy. (Science Daily)
Could Metals Help Treat Cancer? Jul 31, 2008
The currently known CK2 inhibitors are all organic compounds that neutralize enzymatic activity by binding to its active site (3) ... Unlike organic inhibitors, POMs do not bind to the active site of the enzyme ... (3) The active site of an enzyme is a particular region where the substrates bind together and enzymatic reactions takes place. (Science Daily)
Plant-like substitutions in the large-subunit carboxy terminus of Chlamydomonas Rubisco increase CO2/O2 specificity Jul 30, 2008
Nonetheless, because of its positive influence on specificity, the carboxy terminus, relatively far from the active site, may serve as a target for enzyme improvement via combinatorial approaches. The complete article is available as a. (BioMed Central)
Metallic molecules play role in curing cancer Jul 28, 2008
The currently known CK2 inhibitors are all organic compounds that neutralize enzymatic activity by binding to its active site ... Unlike organic inhibitors, POMs do not bind to the active site of the enzyme. (Xinhuanet, China)
Potential New Drug Candidates To Combat 'Bird Flu' Identified Jul 8, 2008
Several looked like particularly good candidates, Amaro said, since they bound to both the regular active site and an additional side pocket that opened during the computer simulation. The general idea is that we will be able to make a better drug through the strategic targeting of multiple active site pockets, said Amaro ... Potential candidate drugs are shown docked into the neuraminidase active site in panels A-D. Panel A shows the crystal structure protein; panels B-D show proteins generated... (Science Daily)
How Cell's Master Transcribing Machine Achieves Near Perfection Jun 7, 2008
Both groups concentrated on the function of the Pol II "active site" region, where the enzyme captures an RNA component, called a nucleosidetriphosphate (NTP), and chemically attaches it to the RNA chain ... In their paper, Kaplan and colleagues explored a key component of the active site known as the "trigger loop." This small bit of protein is highly mobile, and although researchers have believed that it plays a critical function in discriminating the correct NTP, that function was poorly... (Science Daily)
A molecular switch turns on the flame in 'nature's blowtorch' May 30, 2008
In one orientation, both oxygen and the molecule to be oxidized (substrate) can get in and out of the P450 active site, but the oxygen is not "activated," that is, it is not in a state to react with the substrate (or anything else, for that matter) ... After another substrate molecule and oxygen move into the active site, the cycle can repeat. (EurekAlert!)
Compound That Could Lead To New Blood Pressure Drugs Discovered May 4, 2008
"If you consider the structure of an enzyme's active site it's easy to see that if you plug up the active site it's not going to work. But how can one make the enzyme actually work better" This seemed to be a very significant challenge we were probably not likely to overcome. We tried anyway. (Science Daily)
UF scientists discover compound that could lead to new blood pressure drugs May 2, 2008
If you consider the structure of an enzymes active site its easy to see that if you plug up the active site its not going to work. But how can one make the enzyme actually work better" This seemed to be a very significant challenge we were probably not likely to overcome. We tried anyway. And it worked. That in itself is a significant accomplishment because no one has ever specifically identified a compound that enhances the activity of an enzyme using a rational structure-based approach,... (EurekAlert!)
Fox Chase researchers discover a method for clamping down on a cancer-promoting enzyme Apr 19, 2008
The active site where the phosphorylation reaction occurs is an attractive target for drug development, since blocking the active site would deactivate the enzyme. Unfortunately, the active site of PAK1 shares a molecular architecture similar to that found in many other kinase enzymes ... Previous attempts to inhibit the PAK1 active site chemically have also resulted in inhibiting PAK1-related enzymes, with toxic consequences. (EurekAlert!)
Plants Grow Spindly When Reaching For Sunlight: Now Researchers Understand How Apr 9, 2008
"The active site chemically resembled a nook and cranny likely to bind the amino acid tryptophan," says Noel. "That's when it became really exciting since we knew that plants can use tryptophan to synthesize auxin.". (Science Daily)
Birth On An Enzyme: Scientists Succeed In Designing Artificial Enzymes That Also Undergo 'Evolution In A Test Tube' Mar 26, 2008
During the first heat of the 'competition,' the research team designed the 'heart' of the enzymatic machine the active site where the chemical reactions take place ... The scientists found that the mutations occurring in the area surrounding the enzyme s active site caused minor structural changes, which in turn, resulted in an increased chemical reaction rate ... Other mutations increased the flexibility of the enzymes, which helped to increase the speed of substrate release from the active... (Science Daily)
Scientists see Norwalk virus' Achilles heel Mar 19, 2008
The copying, which occurs within an area of the enzyme called an active site, can be blockedor inhibited--with a drug molecule shaped to fit the site, like a key in a key hole. These are the first structures showing the enzyme doing its job interacting with RNA, says Professor Ng. (EurekAlert!)
The structure of resistance Feb 23, 2008
Their report reveals that the enzyme has a flexible active site that can evolve to accommodate new antibiotics, allowing the bacteria to break them down and render them useless. This explains why this type of enzyme is now carried by many bacteria struggling for survival in the antibiotic age. (EurekAlert!)
Structural Study Of Anthrax Yields New Antibiotic Target Feb 5, 2008
So if we could bind a small molecule to the binding site in such a way that it doesn t productively activate it, we could inhibit the activity of the molecule without inhibiting the same active site of mammalian enzymes, Stebbins says. This, he hopes, would result in bacteria that are unable to build their cell walls and therefore would be unable to survive. (Science Daily)
Celiac Disease: Discovery Of Enzyme's Structure May Lead To New Treatments Jan 10, 2008
Now, Chaitan Khosla and colleagues at Stanford University report the first-ever determination of the "open" structure of the enzyme, in which its active site is accessible to substrates. The finding that could help scientists design inhibitors of the enzyme that could serve as medications for celiac disease and other related conditions, according to the article. (Science Daily)
'Wiring Up' Enzymes For Producing Hydrogen In Fuel Cells Nov 22, 2007
8, 1999) A look-alike enzyme active site synthesized by scientists at the University of Illinois may move the world much closer to an energy-efficient, hydrogen-based economy. (Oct. (Science Daily)
Unlocking the function of enzymes Nov 7, 2007
The team started with the three-dimensional X-ray structure of an enzyme and then used a computer to try to fit different smaller molecules into the active site of the enzyme like pieces in a puzzle. Each enzyme has a specific size and shape, Raushel said, and you can use a computer to take small molecules and fit them into the active site of an enzyme one by one and score them on how well they fit. (EurekAlert!)
What Is an Enzyme? Oct 21, 2007
Each enzyme has a unique 3-D shape, including a surface groove called an active site which fits its target substrate much like a lock fits a key. Other substances that don t fit can't enter the active site and no reaction occurs ... Heat denatures, or changes the shape of proteins, and enzyme shape is crucial for the substrate to precisely fit into the active site. (Suite101.com)
Mixing Large Doses Of Common Painkiller And Caffeine May Increase Risk Of Liver Damage Sep 29, 2007
Reference: "Cooperative Binding of Acetaminophen and Caffeine within the P450 3A4 Active Site," tx7000702, Print publication date: Oct. 15, 2007, Online date: 9-26-07. Note: This story has been adapted from material provided by American Chemical Society. (Science Daily)
Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage Sep 26, 2007
Paper: Cooperative Binding of Acetaminophen and Caffeine within the P450 3A4 Active Site, tx7000702 Print publication date: Oct. 15, 2007 ASAP (online) date: 9-26-07. . (EurekAlert!)
ESRF Lightsource Helps Tailoring New Treatments Against Asthma Aug 4, 2007
Bound glutathione, indicating the position of the active site, is in ball and stick representation ... b) Cytosolic view of the trimer, showing the position of the three active sites with loop 1 covering each binding pocket ... The structure finally allows the exact position and characteristics of the active sites, where activating or blocking molecules can bind, to be identified. (Science Daily)
New candidate drug for bipolar disorder Jul 7, 2007
Like most enzyme inhibitors, these compounds seem to stick in the enzyme's 'active site', a kind of cleft in which it binds and transforms its normal target molecules in the cell. So the researchers looked for similar molecules that might be expected to fit more neatly into this specific enzyme's cavity. (Nature News Service)
Translating form into function Jul 2, 2007
Docking works by allowing researchers to first determine the atom-by-atom structure of an enzyme and then screen many thousands of molecules for one that fits into the empty active site of the enzyme ... A molecule that fits the enzymes active site will block its activity just what many promising drugs do ... The strategy works well for one kind of drug discovery -- finding molecules to fit in the active site and physically block enzyme action. (EurekAlert!)
Hepatitis B Drug a Threat to Those with HIV Jun 22, 2007
"The active site [of drug action] -- a polymerase enzyme -- is similar on HIV and hepatitis B," explained the study's lead author, Dr. Chloe Thio, an associate professor of medicine at Johns Hopkins University School of Medicine in Baltimore. Her team tracked changes in HIV levels in the blood, as well as blood counts of CD4 T-cells (a marker of HIV's impact on the immune system) in three men co-infected with hepatitis B and HIV. The patients were using Baraclude to treat their hepatitis B but... (MEDLINEplus)
Nature the druggist Apr 30, 2007
Many small molecules, devoid of three-dimensional stereochemistry, will fit into the active site of an enzyme, or block the function of a receptor, but they do not fit perfectly and they may not be ideal drugs in the long run (as they might also fit in to biochemically related enzymes or receptors that you do not want to block). A human size 10 hand fits perfectly in a size 10 glove, and with only great difficulty can that hand get into a size 5 glove. (The Palm Beach Post)
New 'Biofuel Cell' Produces Electricity From Hydrogen In Plain Air Apr 3, 2007
"We are at the tip of a large iceberg, with important consequences for the future, but there is still much to do before this generation of enzyme-based fuel cells becomes commercially viable. The idea of electricity from hydrogen in air, using an oxygen-tolerant hydrogenase is new, although other scientists have been investigating enzymes as electrocatalysts for years. Most hydrogenases have fragile active sites that are destroyed by even traces of oxygen, but oxygen tolerant hydrogenases have... (Science Daily)
RNA Enzyme Structure Offers A Glimpse Into The Origins Of Life Mar 17, 2007
The active site where ligation occurs is located on one stem, and the structure shows that the molecule folds in such a way that parts of another stem are positioned over the ligation site, forming a pocket where the reaction takes place. A magnesium ion bound to one stem and positioned in the pocket plays an important role in the reaction, Robertson said. (Science Daily)
Researchers Create Artificial Enzyme That Mimics The Body's Internal Engine Mar 17, 2007
To help scientists achieve a better understanding of how CcO works, Collman and his colleagues have built a new model of the enzyme's active site-a region on the protein's surface where chemical reactions occur ... To understand why CcO is so efficient, Collman's group, led by Stanford research associate Richard Decreau, created an artificial version of the enzyme active site using organic compounds as building materials ... This finding led the researchers to conclude that all three active... (Science Daily)
Computer-designed molecule to clean up fluorocarbons? Mar 3, 2007
Instead, the research team applied basic quantum mechanical theory of electron structures in molecules, together with the example of a known molecule that binds to and extracts chlorine ions, to calculate the make-up and geometry of the critical "active site" in the enzyme that does the work. They then designed in software a large ring-shaped molecule to hold those components in just the right orientation to break the C-F bond in methyl fluoride, a simple fluorocarbon. (EurekAlert!)
Advance In Understanding Of Blood Pressure Gene Could Lead To New Treatments Feb 6, 2007
They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: "These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO... (Science Daily)
Findings Could Lead To A Safer And More Effective Method To Control Mosquito-caused Malaria Dec 26, 2006
Most pesticides today work by crippling the serine residue, which is another amino acid of the enzyme acetylcholinesterase and is located at the active site of the enzyme ... He found that the cysteine and arginine residues were located at the opening of the active site of the mosquito acetylcholinesterase ... An active site is a pocket in an enzyme where a fast chemical reaction takes place to break down a molecule or build a new molecule. (Science Daily)
On the activity loss of hydrolases in organic solvents:II. A mechanistic study of subtilisin Carlsberg Dec 23, 2006
Furthermore, active site titration revealed that the number of active sites remained constant during incubation ... Electron paramagnetic resonance spectroscopy studies revealed no substantial increase in the rotational freedom of a paramagnetic nitroxide inhibitor bound to the active site (a spin-label) during incubation in neat 1,4-dioxane, when the water activity was kept constant using BaBr2 hydrated salts ... However, other mechanisms, such as small distortions around the active site or... (BioMed Central)
Night of the living enzyme Nov 29, 2006
It could be that in some cases the active site, the part of the enzyme that needs to be in contact with the chemical to be converted, was pointing the wrong way and pressed tightly against the walls of the pore, Ackerman said. To show that the enzymes were trapped inside the FMS pores, the team stained the protein-FMS complex with gold nanoparticles and documented the enzyme-in-pore complex through electron microscopy. (EurekAlert!)
Scientists Convert Modern Enzyme Into Its Hypothesized Ancestor Nov 1, 2006
View of the axis of the four helix bundle common to diiron proteins showing the castor desaturase T199D active site ... While these enzymes have little in common with more modern biosynthetic enzymes that mediate oxygen chemistry, they share certain structural and sequence characteristics around their active sites -- namely, a pair of iron atoms for binding oxygen within a similar four-helix bundle ... The Brookhaven/Karolinska team had previously performed a structural comparison of the active... (Science Daily)
Structure Of Enzyme Offers Treatment Clues For Diabetes, Alzheimer's Oct 17, 2006
"By revealing IDE's active site in unprecedented detail," notes the commentary, "the new structures provided by Tang and coworkers hold great promise for finally realizing Mirsky's dream.". The National Institutes of Health, the University of Chicago Diabetes Research and Training Center and the American Heart Association funded the study. (Science Daily)
Mayo Clinic study could lead to safer pesticides Oct 13, 2006
It is located at the opening of the active site of acetylcholinesterase ... He discovered the pest-specific cysteine residue located at the edge of the active site of the insect acetylcholinesterase ... Acetylcholinesterase enzymes have a deep and narrow active site. (EurekAlert!)
Chink in the armour of H5N1 bird flu virus Aug 21, 2006
The cavity in the N1 enzyme closes to lock on to target proteins in a cell so the virus can get a foothold and infect it, but a new drug could be designed so that its atoms bind more snugly into this active site than Tamiflu and Relenza do and prevent the cavity from shutting. Such a drug, say the researchers, might avoid the resistance that some influenza viruses have already acquired to Tamiflu. (News-Medical.net)
Structure Of Key Enzyme In Plague Bacterium Found Aug 18, 2006
The active site is believed to lie inside the barrel. (Credit: NIST). (Science Daily)
New Weakness in Avian Flu Virus Found Aug 17, 2006
"The major difference is the presence of a cavity next to the active site of the enzyme. In this group, the cavity is a constant feature.". This suggests that it may be possible to design or identify other compounds that would block neuraminidase activity. (WREG.com, TN)
Chink found in flu virus enzymes Aug 17, 2006
The active site of the N1 neuraminidase enzyme (left) contains an additional cavity missing from some other forms ... Scientists assumed this was because the 'active site' the part of the enzyme that cuts viruses free from cells and also where the drugs bind must be identical in all of the types ... This made sense because the sequences of amino acids in all neu 00000AC8 raminidase active sites are virtually identical. (Nature News Service)
New potential drug target in tuberculosis May 30, 2006
A high-resolution picture of the active site of LipB bound to a lipid inhibitor helped to determine the function of the enzyme ... "LipB is a very promising drug target," Wilmanns says, "because it belongs to a vital pathway. Unlike other organisms M. tuberculosis has no backup mechanism that could take over LipB's role. This means that an inhibitor blocking its active site would shut down key processes the bacterium needs to survive and replicate. This would be a very effective strategy for a... (EurekAlert!)
Computer simulation hints at new HIV drug target Mar 11, 2006
"They helped in the discovery of the current HIV protease inhibitors, which bind to the active site of the enzyme. They were also key to the development of potential inhibitors of the third enzyme associated with HIV, the integrase enzyme. "Other simulations by our group discovered an unknown binding site on the integrase enzyme, " McCammon explained. "Merck's new anti-integrase inhibitors include molecules that are designed to hit that site, in addition to a site that was known earlier from... (EurekAlert!)
Studies Suggest New Targets For Tuberculosis Treatments Mar 8, 2006
These studies revealed highly specific details of the proteasome active site and mechanism, which will be invaluable to designing TB specific inhibitors. The proteasome structure was revealed by Guiqing Hu and collaborators using cryo electron microscopy in Brookhaven Lab s Biology Department and by x-ray crystallography at the Lab s National Synchrotron Light Source. (Science Daily)
Modeling the molecules making microRNA Jan 27, 2006
Additionally, we identified a La-like predicted RNA binding domain located C-terminally to the DSRM domain and a domain with a peptide prolyl cis/trans isomerase (PPIase) fold, but without the conserved PPIase active site, located N-terminally to the catalytic domain ... The structural model was used as a platform to identify the putative active site and substrate-binding residues of HEN and to propose its mechanism of action. (BioMed Central)
