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NIH funds multicenter 'glue grant' to study enzyme function
Date:5/21/2010

at exist in nature," says Dr. Almo. "It will also further our understanding of disease and help us identify new targets for drug development."

The leader of the research team is John A. Gerlt, Ph.D., Gutgsell Chair and professor of biochemistry and of chemistry and biophysics at the University of Illinois at Urbana-Champaign. Dr. Gerlt and his colleagues have pioneered diverse techniques for more efficiently determining the function of an enzyme by defining its substrate the molecule to which the enzyme docks to start a reaction. Their approaches involve both computational methods to narrow the substrate candidates and direct experimental screening of potential substrates.

For the EFI Glue Grant, Dr. Gerlt has assembled a team of researchers from several disciplines to discover the function of enzymes an effort that begins with determining the structure of an enzyme of interest. The team will then use computers to create a short "hit list" of possible substrates that are most compatible with the structure of this enzyme. Next, scientists with expertise in particular enzyme superfamilies will evaluate the list to pinpoint the substrate, thereby providing direct insight into the enzyme's function. Then, using a range of bacterial model systems, researchers will "knock out" the gene that codes for this enzyme. The manner in which the loss of this enzyme affects the organism will provide further information about the enzyme's function.

Dr. Almo and his colleagues will be responsible for purifying the enzymes and then using x ray crystallography to determine their molecular structure. (X-ray crystallography is a method that reveals the arrangement of atoms within a protein by striking the protein crystal with a beam of x-rays.) Dr. Almo's team includes Ronald D. Seidel, Ph.D., associate in biochemistry and associate director of the Albert Einstein Macromolecular Therapeutics Development Facility.


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Contact: Deirdre Branley
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine
Source:Eurekalert

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