This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Bacterial biosynthesis of lysine forms an attractive target for the design of new antimicrobial agents because this pathway is indispensable for bacteria and is absent in humans. We have undertaken structural investigations on enzyme targets involved in the biosynthesis of lysine from bacterial pathogens and plants. Crystal structures of two of these enzymes, namely, diaminopimelate epimerase from Haemophilus influenzae and LL-diaminopimelate aminotransferase from Arabidopsis thaliana have been determined recently. Structural work is continuing on these enzymes in complex with inhibitors and of mutant forms to understand details of the catalytic mechanism for the design of effective inhibitors. Recently, we have obtained crystals of the diaminopimelate epimerase from Arabidopsis. Also, crystallization trials are currently underway on the diaminopimelate aminotransferase from the human pathogen, Chlamydia. We have an ongoing collaboration for high-throughput screening of 80,000 chemical compounds in order to find potential inhibitor leads for crystallographic analysis in our drug design efforts against Chlamydial infections. Other targets undergoing crystallization trials include diaminopimelate desuccinylase from the tuberculosis causing mycobacteria. In order to achieve the best possible resolution and quality of diffraction data, as well as for de novo structure solution using MAD/SAD methods, we require access to the synchrotron beamlines for macromolecular crystallography.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-32
Application #
8362184
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (40))
Project Start
2011-03-01
Project End
2012-02-29
Budget Start
2011-03-01
Budget End
2012-02-29
Support Year
32
Fiscal Year
2011
Total Cost
$810
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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