CONFORMATIONAL CHANGES OF ENZYME GLUTAMATE RACEMASE BY SAXS & WAXS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bacillus anthracis has been classified by the Centers for Disease Control and Prevention as a high-priority, category A agent, based upon its potential for causing mass casualties in the event of a bioterrorist attack. The ability of microbes to acquire antibiotic resistance, as well as the feasibility of selecting multi-drug resistant strains of anthrax, has created a need for novel antimicrobial drugs that target these lethal bacteria. Glutamate racemase (RacE) is responsible for converting L-glutamate to D-glutamate, which is an essential component of peptidoglycan biosynthesis. RacE enzymes are essential for bacterial growth, and they lack a human homolog making them attractive targets for the design and development of antibacterial therapeutics. There are two putative glutamate racemase isozymes, RacE1 and RacE2, in the B. anthracis genome. Studies indicate that RacE1, in solution, is a monomer in the absence of substrate but dimerizes when substrate is present. RacE2 is a dimer irrespective of the presence of substrate. The crystal structures of these enzymes bound to substrate indicate that they should have an open and a closed conformation and should therefore undergo significant conformational changes in solution. Solution scattering experiments will help us answer the following questions- (1) what are the conformational changes that these enzymes undergo during catalysis (2) how is the process of dimerization for RacE1 connected with catalysis. This information will help us obtain a better understanding of the conformations of these enzymes in solution which will guide us through the structure based drug design process.