Cancer metabolism discovery uncovers new role of IDH1 gene mutation in brain cancer Nov 23, 2009
Through a mix of large-scale profiling of hundreds of cellular metabolites, x-ray crystallography, and innovative enzymology, the Agios team demonstrated that a single amino-acid substitution in the IDH1 active site allows the enzyme to acquire an entirely new activity to produce the metabolite 2HG. Analysis of tumor samples of brain cancer patients with the IDH1 mutation revealed up to hundred-fold elevations in concentrations of 2HG, a metabolite that has been previously linked to the... (EurekAlert!)
Zap! Light used to paralyze tiny creatures Nov 21, 2009
"For instance, we've demonstrated a photoswitch that changed shape, and in one form, it fit into the active site of an enzyme really well, controlling its activity, while in its other form, it was too big to fit into that site," Branda said. "For any clinical applications, we wouldn't want to use , which can damage tissues.". (MSNBC -- Environment)
Venomous Shrew, Lizard: Enzyme Evolved Twice Nov 2, 2009
Enzymes are proteins that catalyze, or increase the rates of, chemical reactions; this rate enhancement occurs at a specific region on an enzyme called the active site. Aminetzach found that the specific molecular differences between kallikrein and its toxic descendent are highly localized around the enzyme's active site ... "The active site is physically opened up, and the loops surrounding it become more flexible. The area around the active site also becomes positively charged, serving to... (Science Daily)
Scientists Are First To Observe The Global Motions Of An Enzyme Copying DNA Oct 30, 2009
"By moving away from the DNA, the additional space on the enzyme's active site may accommodate a distorted DNA structure," Suo said. "We are investigating that possibility now.". (Science Daily)
Inhibitors Of Important Tuberculosis Survival Mechanism Identified Oct 13, 2009
The structural studies revealed that the inhibitor molecules block the proteasome s ability to degrade proteins in more than one way: by producing a direct chemical change to the proteasome active site, and by altering the conformation of the pocket into which protein fragments bind before being degraded ... The many amino acid residues of the TB proteasome involved in this conformational change, some far away from the active site, are different from those in human proteasomes. (Science Daily)
Ironing out the genetic cause of hemoglobin problems Oct 12, 2009
Second, the paper includes evidence for how the genetic variant affects TMPRSS6 function at a molecular level, and shows that the genetic variation causes an amino acid change near the enzyme's active site, that is likely to affects the way TMPRSS6 reacts with target molecules. . (EurekAlert!)
Hydrogen-making Algae's 'Achilles' Heel' Discovered Oct 2, 2009
Because oxygen is a major by-product of the hydrogen-making photosynthetic process in such organisms, the build-up of oxygen, which rapidly attacks the active site of the enzyme, quickly brings the hydrogen-making process to an irreversible halt ... The team used electrochemical kinetic methods to determine the order of events in which oxygen attacks the active site of an iron-iron hydrogenase found in the green algae Chlamydomonas reinhardtii ... By measuring ripples in the photoelectron energy... (Science Daily)
New Antituberculosis Compounds Discovered Sep 17, 2009
The structural studies revealed that the inhibitor molecules block the proteasome's ability to degrade proteins in more than one way: by producing a direct chemical change to the proteasome active site, and by altering the conformation of the "pocket" into which protein fragments bind before being degraded ... "The many amino acid residues of the TB proteasome involved in this conformational change, some far away from the active site, are different from those in human proteasomes. This might... (Science Daily)
Enzyme inhibitor takes an unexpected approach toward blocking cancer-promoting protein Sep 8, 2009
"Typically, research has focused on ways of blocking the active site of enzymes, the part of the enzyme that performs a particular task," says Jeffrey R. Peterson, Ph ... "The structure of active site, however, is often shared among kinases, which makes it tough to target a particular kinase without accidentally inhibiting a related enzyme." ... The idea is not entirely without precedent, the cancer drug Gleevec, for example, is unusually selective for its target by binding to a region outside... (EurekAlert!)
New Drug Target For Kaposi's Sarcoma Aug 3, 2009
Most current antiviral drugs target the active sites of viral proteins, where enzymes and receptors work in a lock-and-key approach to either activate or deactivate that particular protein, the researchers explained ... The HIV protease was successfully targeted for drug development in the 1980s, by blocking the active site on the surface of the dimer, but the herpes virus protease dimer has consistently eluded efforts to disrupt it at its active site, the researchers said ... To their... (Science Daily)
'Corrective genes' closer thanks to enzyme modification Jul 29, 2009
The paper, "Multiple Conformers in Active Site of Human Dihydrofolate Reductase F31R/Q35E Double Mutant Suggest Structural Basis for Methotrexate Resistance," published in The Journal of Biological Chemistry, was authored by Jordan P. Volpato, Elena Fossati Jonathan Blanchet, Lucie Poulin, Vanessa Guerrero and Joelle N. Pelletier of the Universit de Montral; Brahm J. Yachnin and Albert M. Berghuis of McGill University. On the web. (EurekAlert!)
New Target For Tailored Antibiotics Discovered Jul 22, 2009
wert s research team have now succeeded in cracking the closed state X-ray crystal structure that shows the precise folding pattern of the protein chain and the chemical environment of the active site cavity. The crystal structure opened the door to a detailed examination of the reaction mechanism using computer simulation and mutagen experiments in which Escherichia coli bacteria are coerced into synthesizing defective IspH enzymes. (Science Daily)
Structural Biology Scores With Protein Snapshot Jul 13, 2009
The DAGK structure, Sanders said, "confirmed that this is a really strange kinase." The enzyme has a porch-like structure, with a wide opening for its substrate diacylglycerol and the active site at the top of the porch. "The active site looks nothing like any other kinase active site it's a unique architecture," Sanders said ... The researchers also performed exhaustive mutagenesis studies in which they characterized mutations at each amino acid in DAGK and used the data to map the active site... (Science Daily)
Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases Jul 4, 2009
The crystal structure of PvPNP is described and is seen to have many features in common with the previously reported structure of PfPNP. In particular, the composition and conformations of the active site regions are virtually identical. The crystal structure of a complex of PfPNP co-crystallised with inosine and arsenate is also described, and is found to contain a mixture of products and reactants - hypoxanthine, ribose and arsenate. (BioMed Central)
Scientists discover new chemical reaction for DNA production in bacteria and viruses Apr 17, 2009
In particular, the team identified that the first step of the FTDS-catalyzed reaction involves the transfer of a proton and two electrons, known as a hydride, from a flavin co-factor molecule to dUMP whereas the first step of the TS-catalyzed reaction involves an amino acid from the enzyme's active site forming a bond with dUMP.. "This work nicely illustrates how chemists using traditional techniques and contemporary instrumentation methods can make substantial contributions to important and... (EurekAlert!)
Discovery Of Tuberculosis Bacterium Enzyme Paves Way For New TB Drugs Apr 2, 2009
Regulation of active site coupling in glutamine-dependent NAD+ synthetase was written by Nicole LaRonde-LeBlanc, Melissa Resto, and Barbara Gerratana ... LaRonde-LeBlanc et al. Regulation of active site coupling in glutamine-dependent NAD synthetase ... Close up of the glutamine and ammonia tunnels shown in white surface connecting the glutaminase and synthetase active sites from two different subunits. (Science Daily)
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2) Feb 24, 2009
75 A resolution, which reveals that imatinib binds in the enzyme active site, adjacent to the flavin isoalloxazine ring ... The structure of the imatinib-NQO2 complex demonstrates that imatinib inhibits NQO2 activity by competing with substrate for the active site ... Interactions made by imatinib with residues at the rim of the active site provide an explanation for the binding selectivity of NQO2 for imatinib, nilotinib, and dasatinib. (BioMed Central)
Inhibiting Proteins May Prevent Cartilage Breakdown In Arthritis Patients Feb 20, 2009
In this study, researchers identified an active site in the SAF-1 protein molecule that is involved in the interaction with AP-1 to induce the expression of the MMP-1 gene. In this study, we looked at how and why MMP-1 is activated, particularly in the disease condition, Ray said. (Science Daily)
New Method Monitors Critical Bacteria In Wastewater Treatment Feb 14, 2009
The researchers used their new technique to verify a theory proposed decades ago that copper at the enzyme's "active site" where ammonia binds is critical to enabling the conversion ... "So, by doing an experiment where we can turn biochemical switches on and off in the bacteria we have validated the fact that copper is indeed at the active site, while at the same time demonstrating the power of this monitoring technique.". (Science Daily)
How Influenza Virus Hijacks Human Cells Feb 14, 2009
The high-resolution image of the domain reveals the individual amino acids that constitute the active site responsible for cleaving the RNA; information that could guide the design of future antiviral drugs ... The active site responsible for RNA cleavage is shown in red. (Science Daily)
Malaria Breakthrough Starves Parasite Feb 7, 2009
The "drug" is shown in magenta and is bound in the active site. (Credit: Image courtesy of Monash University). (Science Daily)
