5UHU

Solution conformation of cytochrome P450 MycG with mycinamicin IV bound

5UHU の概要

• エントリーDOI: 10.2210/pdb5uhu/pdb
• 関連するPDBエントリー: 2Y98
• NMR情報: BMRB: 26750
• 分子名称: Mycinamicin IV hydroxylase/epoxidase, PROTOPORPHYRIN IX CONTAINING FE, MYCINAMICIN IV, ... (4 entities in total)
• 機能のキーワード: antibiotic biosynthesis, oxidoreductase
• 由来する生物種: Micromonospora griseorubida
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45697.78

構造登録者

Pochapsky, T.C.,Tietz, D.R. (登録日: 2017-01-12, 公開日: 2017-08-23, 最終更新日: 2024-05-01)

主引用文献

Tietz, D.R.,Podust, L.M.,Sherman, D.H.,Pochapsky, T.C.
Solution Conformations and Dynamics of Substrate-Bound Cytochrome P450 MycG.
Biochemistry, 56:2701-2714, 2017

PubMed Abstract: MycG is a P450 monooxygenase that catalyzes the sequential hydroxylation and epoxidation of mycinamicin IV (M-IV), the last two steps in the biosynthesis of mycinamicin II, a macrolide antibiotic isolated from Micromonospora griseorubida. The crystal structure of MycG with M-IV bound was previously determined but showed the bound substrate in an orientation that did not rationalize the observed regiochemistry of M-IV hydroxylation. Nuclear magnetic resonance paramagnetic relaxation enhancements provided evidence of an orientation of M-IV in the MycG active site more compatible with the observed chemistry, but substrate-induced changes in the enzyme structure were not characterized. We now describe the use of amide H-N residual dipolar couplings as experimental restraints in solvated "soft annealing" molecular dynamics simulations to generate solution structural ensembles of M-IV-bound MycG. Chemical shift perturbations, hydrogen-deuterium exchange, and N relaxation behavior provide insight into the dynamic and electronic perturbations in the MycG structure in response to M-IV binding. The solution and crystallographic structures are compared, and the possibility that the crystallographic orientation of bound M-IV represents an inhibitory mode is discussed.

PubMed: 28488849
DOI: 10.1021/acs.biochem.7b00291

実験手法

SOLUTION NMR