Work

Detection of a Geminate Photoproduct of Bovine Cytochrome c Oxidase by Time-Resolved Serial Femtosecond Crystallography

Year: 2023

Type: article

Abstract: Cytochrome c oxidase (C c O) is a large membrane-bound hemeprotein that catalyzes the reduction of dioxygen to water. Unlike classical dioxygen binding hemeproteins with a heme b group in their active sites, C c O has a unique binuclear center (BNC) comprised of a copper atom (Cu B ) and a heme a 3 iron, where O 2 binds and is reduced to water. CO is a versatile O 2 surrogate in ligand binding and escape reactions. Previous time-resolved spectroscopic studies of the CO complexes of bovine C c O (bC c O) revealed that photolyzing CO from the heme a 3 iron leads to a metastable intermediate (Cu B -CO), where CO is bound to Cu B , before it escapes out of the BNC. Here, with a time-resolved serial femtosecond X-ray crystallography-based pump-probe method, we detected a geminate photoproduct of the bC c O-CO complex, where CO is dissociated from the heme a 3 iron and moved to a temporary binding site midway between the Cu B and the heme a 3 iron, while the locations of the two metal centers and the conformation of the Helix-X, housing the proximal histidine ligand of the heme a 3 iron, remain in the CO complex state. This new structure, combined with other reported structures of bC c O, allows the full definition of the ligand dissociation trajectory, as well as the associated protein dynamics.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.3c07803

Authors: Izumi Ishigami, Sergio Carbajo, Nadia Zatsepin, Masahide Hikita, Chelsie E. Conrad, Garrett Nelson, Jesse Coe, Shibom Basu, Thomas Grant, Matthew H. Seaberg, Raymond G. Sierra, Mark S. Hunter, Petra Fromme, Raimund Fromme, Denis L. Rousseau, Syun-Ru Yeh

Institutions: Albert Einstein College of Medicine, University of California, Los Angeles, SLAC National Accelerator Laboratory, Linac Coherent Light Source, La Trobe University, Arizona State University, University at Buffalo, State University of New York

Language: English

Topic: Metal-Catalyzed Oxygenation Mechanisms

Subfield: Inorganic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Science Foundation, U.S. Department of Energy, Arizona State University, National Institutes of Health, Office of Science, NIH Office of the Director, National Institute of General Medical Sciences, National Center for Research Resources, Division of Chemistry, Division of Biological Infrastructure, National Center for Advancing Translational Sciences, Basic Energy Sciences, SLAC National Accelerator Laboratory

Awards: G1229526393, G1286251239, G1804828992, G2371548206, G2393997808, G262532246, G303061748, G3488436650, G3629260272, G4235786860, A Synchroton Radiation Structural Biology Resource, G4280418065, G495301720, G4978942704, G498139845, G5376940358, G5570207115, Dynamics of membrane proteins unraveled by time-resolved serial crystallography, G5637119208, G6550344761, Structure and Function of Heme-based Dioxygenases, G7214672632, G7283024673, G7288961653, High-end X-ray Detector System for Femtosecond Crystallography, ABI Innovation: New Algorithms for Biological X-ray Free Electron Laser Data, G8382000481, Reactive Intermediates in cytochrome oxidase, A Synchrotron Radiation Structural Biology Resource, G8925327636, Structures of intermediates in cytochrome c oxidase, Structural Dynamics at LCLS, G911061179, Biology with X-ray Lasers, G969889393

OpenAlex ID: W4386593239

FWCI: 0.584

Cites: 31

Cited by: 8

Related to: 10