5WEH

Cytochrome c oxidase from Rhodobacter sphaeroides in the reduced state

Summary for 5WEH

• Entry DOI: 10.2210/pdb5weh/pdb
• Descriptor: Cytochrome c oxidase subunit 1, DODECYL-ALPHA-D-MALTOSIDE, Cytochrome c oxidase subunit 2, ... (11 entities in total)
• Functional Keywords: oxidase, complex iv, reduced, oxidoreductase
• Biological source: Rhodobacter sphaeroides; More
• Total number of polymer chains: 8
• Total formula weight: 269754.03

Authors

Liu, J.,Ferguson-Miller, F.,Ling, Q.,Hiser, C. (deposition date: 2017-07-10, release date: 2017-09-13, Last modification date: 2024-10-23)

Primary citation

Liu, J.,Hiser, C.,Ferguson-Miller, S.
Role of conformational change and K-path ligands in controlling cytochrome c oxidase activity.
Biochem. Soc. Trans., 45:1087-1095, 2017

PubMed Abstract: Given the central role of cytochrome oxidase (CO) in health and disease, it is an increasingly important question as to how the activity and efficiency of this key enzyme are regulated to respond to a variety of metabolic states. The present paper summarizes evidence for two modes of regulation of activity: first, by redox-induced conformational changes involving the K-proton uptake path; and secondly, by ligand binding to a conserved site immediately adjacent to the entrance of the K-path that leads to the active site. Both these phenomena highlight the importance of the K-path in control of CO. The redox-induced structural changes are seen in both the two-subunit and a new four-subunit crystal structure of bacterial CO and suggest a gating mechanism to control access of protons to the active site. A conserved ligand-binding site, first discovered as a bile salt/steroid site in bacterial and mammalian oxidases, is observed to bind an array of ligands, including nucleotides, detergents, and other amphipathic molecules. Highly variable effects on activity, seen for these ligands and mutations at the K-path entrance, can be explained by differing abilities to inhibit or stimulate K-path proton uptake by preventing or allowing water organization. A new mutant form in which the K-path is blocked by substituting the conserved carboxyl with a tryptophan clarifies the singularity of the K-path entrance site. Further study in eukaryotic systems will determine the physiological significance and pharmacological potential of ligand binding and conformational change in CO.

PubMed: 28842531
DOI: 10.1042/BST20160138

Experimental method

X-RAY DIFFRACTION (3.45 Å)