5MNS

Structural and functional characterization of OleP in complex with 6DEB in sodium formate

Summary for 5MNS

• Entry DOI: 10.2210/pdb5mns/pdb
• Descriptor: Cytochrome P-450, PROTOPORPHYRIN IX CONTAINING FE, 6-DEOXYERYTHRONOLIDE B, ... (4 entities in total)
• Functional Keywords: p450, cytochrome, 6deb, epoxidase, oxidoreductase
• Biological source: Streptomyces antibioticus
• Total number of polymer chains: 6
• Total formula weight: 276090.48

Authors

Parisi, G.,Savino, C.,Montemiglio, L.C.,Vallone, B. (deposition date: 2016-12-13, release date: 2018-02-28, Last modification date: 2024-01-17)

Primary citation

Parisi, G.,Montemiglio, L.C.,Giuffre, A.,Macone, A.,Scaglione, A.,Cerutti, G.,Exertier, C.,Savino, C.,Vallone, B.
Substrate-induced conformational change in cytochrome P450 OleP.
FASEB J., 33:1787-1800, 2019

PubMed Abstract: The regulation of cytochrome P450 activity is often achieved by structural transitions induced by substrate binding. We describe the conformational transition experienced upon binding by the P450 OleP, an epoxygenase involved in oleandomycin biosynthesis. OleP bound to the substrate analog 6DEB crystallized in 2 forms: one with an ensemble of open and closed conformations in the asymmetric unit and another with only the closed conformation. Characterization of OleP-6DEB binding kinetics, also using the P450 inhibitor clotrimazole, unveiled a complex binding mechanism that involves slow conformational rearrangement with the accumulation of a spectroscopically detectable intermediate where 6DEB is bound to open OleP. Data reported herein provide structural snapshots of key precatalytic steps in the OleP reaction and explain how structural rearrangements induced by substrate binding regulate activity.-Parisi, G., Montemiglio, L. C., Giuffrè, A., Macone, A., Scaglione, A., Cerutti, G., Exertier, C., Savino, C., Vallone, B. Substrate-induced conformational change in cytochrome P450 OleP.

PubMed: 30207799
DOI: 10.1096/fj.201800450RR

Experimental method

X-RAY DIFFRACTION (2.62 Å)