Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors
- L. Podust, T. Poulos, M. Waterman
- Biology, ChemistryProceedings of the National Academy of Sciences…
- 13 March 2001
Mapping mutations identified in Candida albicans azole-resistant isolates indicates that azole resistance in fungi develops in protein regions involved in orchestrating passage of CYP51 through different conformational stages along the catalytic cycle rather than in residues directly contacting fluconazole.
Two approaches to discovering and developing new drugs for Chagas disease.
- J. McKerrow, P. Doyle, C. Craik
- BiologyMemórias do Instituto Oswaldo Cruz
- 1 July 2009
This review will focus on two general approaches carried out at the Sandler Center, University of California, San Francisco, to address the challenge of developing new drugs for the treatment of…
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest‐4‐en‐3‐one
- H. Ouellet, S. Guan, P. D. de Montellano
- BiologyMolecular Microbiology
- 1 August 2010
CYP125A1 is a key enzyme in cholesterol metabolism and plays a crucial role in circumventing the deleterious effect of cholest‐4‐en‐3‐one.
The Structural Basis for Substrate Anchoring, Active Site Selectivity, and Product Formation by P450 PikC from Streptomyces venezuelae*
- D. Sherman, Shengying Li, L. Podust
- Chemistry, BiologyJournal of Biological Chemistry
- 8 September 2006
Four x-ray crystal structures and allied functional studies for PikC, the remarkable P450 monooxygenase responsible for production of a number of related macrolide products from the Pik pathway, reveal that PikC substrate tolerance and product diversity result from a combination of alternative anchoring modes rather than an induced fit mechanism.
Identification of amino acids in rat pregnane X receptor that determine species-specific activation.
Homology modeling derived from the recently determined crystal structure of human PXR indicates that these amino acids are located within or neighboring the flexible loop that forms part of the pore to the ligand-binding cavity as a critical modulator of PxR response.
Structural Characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole
- Chiung-Kuang J. Chen, S. Leung, C. Guilbert, M. Jacobson, J. McKerrow, L. Podust
- Biology, MedicinePLoS Neglected Tropical Diseases
- 1 April 2010
These studies define in structural detail the CYP51 therapeutic target in T. cruzi, and offer a starting point for rationally designed anti-Chagasic drugs with improved efficacy and reduced toxicity.
Crystal Structure of the CCAAT Box/Enhancer-binding Protein β Activating Transcription Factor-4 Basic Leucine Zipper Heterodimer in the Absence of DNA*
- L. Podust, A. Krezel, Youngchang Kim
- ChemistryJournal of Biological Chemistry
- 5 January 2001
The results suggest that the degree of ordering of the basic region and the fork and the dimerization properties of the leucine zipper combine to distinguish the structurally similar bZIP domains of ATF4 and C/EBPβ with respect to DNA target sequence.
A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases.
- D. Lamb, Youngchang Kim, L. Podust
- Biology, ChemistryStructure
- 2006
Mycobacterium Tuberculosis Cyp130:Crystal Mycobacterium Tuberculosis Cyp130: Crystal Structure, Biophysical Characterization, and Interactions with Antifungal Azole Drugs.
- H. Ouellet, L. Podust, P. O. D. Montellano
- Biology
- 18 December 2007
The 1.92-Å Structure of Streptomyces coelicolor A3(2) CYP154C1
- L. Podust, Youngchang Kim, M. Waterman
- Biology, ChemistryJournal of Biological Chemistry
- 4 April 2003
High sequence similarity to macrolide monooxygenases from other microbial species translates into catalytic activity of CYP154C1 toward both 12- and 14-membered ring macrolactonesin vitro.
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