Abstract

The long range goal of this project is to study structure-function relationships in cytochromes P450 and related proteins using x-ray crystallography, molecular biology, and biochemistry. This competitive renewal focuses on the following areas: a newly discovered P450 called P450cin that has the unusual property of using an FMN-containing protein as the electron donor; oxy-complexes of various P450s and mutants; conformational dynamics in P450BM3 and; heme oxygenase. These various projects address the structure of important intermediates in the catalytic cycle for both P450 and heme oxygenase. Redox complexes will be studied using kinetics and crystallography, in addition to NMR spectroscopy using the new 800MHz instrument recently installed at UCI.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033688-22
Application #
7029731
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Basavappa, Ravi
Project Start
1987-03-01
Project End
2009-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
22
Fiscal Year
2006
Total Cost
$312,412
Indirect Cost

  Institution

Name
University of California Irvine
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Kaur, Parminder; Chamberlin, A Richard; Poulos, Thomas L et al. (2016) Structure-Based Inhibitor Design for Evaluation of a CYP3A4 Pharmacophore Model. J Med Chem 59:4210-20
Poulos, Thomas L (2014) Heme enzyme structure and function. Chem Rev 114:3919-62
Sevrioukova, Irina F; Poulos, Thomas L (2014) Ritonavir analogues as a probe for deciphering the cytochrome P450 3A4 inhibitory mechanism. Curr Top Med Chem 14:1348-55
Madrona, Yarrow; Hollingsworth, Scott A; Tripathi, Sarvind et al. (2014) Crystal structure of cindoxin, the P450cin redox partner. Biochemistry 53:1435-46
Batabyal, Dipanwita; Li, Huiying; Poulos, Thomas L (2013) Synergistic effects of mutations in cytochrome P450cam designed to mimic CYP101D1. Biochemistry 52:5396-402
Tripathi, Sarvind; Li, Huiying; Poulos, Thomas L (2013) Structural basis for effector control and redox partner recognition in cytochrome P450. Science 340:1227-30
Poulos, Thomas L; Madrona, Yarrow (2013) Oxygen activation and redox partner binding in cytochromes P450. Biotechnol Appl Biochem 60:128-33
Batabyal, Dipanwita; Poulos, Thomas L (2013) Crystal structures and functional characterization of wild-type CYP101D1 and its active site mutants. Biochemistry 52:8898-906
Sevrioukova, Irina F; Poulos, Thomas L (2013) Dissecting cytochrome P450 3A4-ligand interactions using ritonavir analogues. Biochemistry 52:4474-81
Sevrioukova, Irina F; Poulos, Thomas L (2013) Pyridine-substituted desoxyritonavir is a more potent inhibitor of cytochrome P450 3A4 than ritonavir. J Med Chem 56:3733-41

Showing the most recent 10 out of 68 publications