Hexapeptide repeat proteins display tandem repeated copies of a six- residue amino acid sequence generally described as (LIV)-(GAED)-X2- (STAV)-X. These proteins display a unique three-dimensional structural motif termed a Left-Handed Parallel beta Helix (LbetaH). Hexapeptide enzymes frequently function as acyltransferases in a variety of processes, including bacterial cell wall biosynthesis, amino acid metabolism and antibiotic inactivation. In this proposal, the three- dimensional structure of at least two members of the largest class of these proteins, the hexapeptide acetyltransferases, will be determined by x-ray crystallography in the presence and absence of ligands. This structural information will be combined with steady state kinetic data in order to define the order of addition of substrates, the identity of catalytically important functional groups and the chemical mechanism of action of these enzymes. This information will be used to characterize the function of this newly recognized superfamily of enzymes and to provide a structural and mechanistic framework for the design of antibiotics directed against bacterial pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI042154-03
Application #
6124348
Study Section
Biochemistry Study Section (BIO)
Project Start
1997-12-01
Project End
2002-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
3
Fiscal Year
2000
Total Cost
$224,383
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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