Gram-positive bacteria adhere to specific tissues in animals using the surface proteins displayed on their cell wall. These surface proteins promote bacterial adhesion, evasion of the host immune system and invasion of the host organism. The enzymes responsible for attaching these proteins to the cell wall are called sortases and they are found in all gram-positive bacteria. The focus of this proposal is to study sortase A (SrtA) from Staphylococcus aureus. To obtain a better understanding of the universal anchoring mechanism of sortases we will design and test the enzymatic effectiveness of several inhibitors of SrtA. We also propose to elucidate the structure of the SrtA-inhibitor complex by using NMR spectroscopy. We will identify the amino acids that are important for catalysis and substrate binding by introducing single amino acid mutations in SrtA. The knowledge gained from this study will hopefully lead to ways of disabling this anchoring mechanism and thereby preventing bacterial infection. Work leading to the creation of anti-infective agents against pathogenic bacteria should be prioritized especially in an era where bacteria have developed a resistance to many commonly used antibiotics. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI061886-02
Application #
6929731
Study Section
Special Emphasis Panel (ZRG1-CDF-1 (29))
Program Officer
Hernandez, Milton J
Project Start
2004-07-15
Project End
2008-07-14
Budget Start
2005-07-15
Budget End
2006-07-14
Support Year
2
Fiscal Year
2005
Total Cost
$29,209
Indirect Cost
Name
University of California Los Angeles
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095