Bacteria are evolving immunity to the current generation of antibiotic drugs, raising the need for new drugs and new drug targets. This proposal presents a plan for the structural determination of one such target, the Zn-dependent UDP-3-O-(R-hydroxymyristoyl)-N- acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus. LpxC catalyzes the first committed step in the synthesis of lipid A, the membrane anchor of the principle component of the outer membrane of E. coli and other Gram-negative bacteria. Inhibited lipid A production either kills bacteria or renders them permeable to antibiotics that are normally blocked from entry into the cell. An X-ray crystal structure of LpxC will allow identification of the key features involved in substrate binding and zinc ion coordination, which in turn will aid in the development of new therapeutics that may be bactericidal alone or in conjunction with other known antibiotics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI010648-01A1
Application #
6405761
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Korpela, Jukka K
Project Start
2001-06-01
Project End
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
1
Fiscal Year
2001
Total Cost
$33,260
Indirect Cost
Name
University of Pennsylvania
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104