4TRI

X-ray crystal structure of CYP142A2 from Mycobacterium smegmatis, complexed with cholesterol sulfate.

4TRI の概要

• エントリーDOI: 10.2210/pdb4tri/pdb
• 分子名称: P450 heme-thiolate protein, PROTOPORPHYRIN IX CONTAINING FE, CHOLEST-5-EN-3-YL HYDROGEN SULFATE, ... (5 entities in total)
• 機能のキーワード: cytochrome p450, cholesterol sulfate, ligand bound, oxidoreductase
• 由来する生物種: Mycobacterium smegmatis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93910.62

構造登録者

Madrona, Y.,Ortiz de Montellano, P. (登録日: 2014-06-17, 公開日: 2014-09-17, 最終更新日: 2023-12-27)

主引用文献

Frank, D.J.,Madrona, Y.,Ortiz de Montellano, P.R.
Cholesterol ester oxidation by mycobacterial cytochrome p450.
J.Biol.Chem., 289:30417-30425, 2014

PubMed Abstract: Mycobacteria share a common cholesterol degradation pathway initiated by oxidation of the alkyl side chain by enzymes of cytochrome P450 (CYP) families 125 and 142. Structural and sequence comparisons of the two enzyme families revealed two insertions into the N-terminal region of the CYP125 family (residues 58-67 and 100-109 in the CYP125A1 sequence) that could potentially sterically block the oxidation of the longer cholesterol ester molecules. Catalytic assays revealed that only CYP142 enzymes are able to oxidize cholesteryl propionate, and although CYP125 enzymes could oxidize cholesteryl sulfate, they were much less efficient at doing so than the CYP142 enzymes. The crystal structure of CYP142A2 in complex with cholesteryl sulfate revealed a substrate tightly fit into a smaller active site than was previously observed for the complex of CYP125A1 with 4-cholesten-3-one. We propose that the larger CYP125 active site allows for multiple binding modes of cholesteryl sulfate, the majority of which trigger the P450 catalytic cycle, but in an uncoupled mode rather than one that oxidizes the sterol. In contrast, the more unhindered and compact CYP142 structure enables enzymes of this family to readily oxidize cholesteryl esters, thus providing an additional source of carbon for mycobacterial growth.

PubMed: 25210044
DOI: 10.1074/jbc.M114.602771

実験手法

X-RAY DIFFRACTION (2 Å)