7cp5
Bovine heart cytochrome c oxidase in a catalytic intermediate of E at 1.76 angstrom resolutionBovine heart cytochrome c oxidase in a catalytic intermediate of E at 1.76 angstrom resolution
Structural highlights
FunctionCOX1_BOVIN Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. CO I is the catalytic subunit of the enzyme. Electrons originating in cytochrome c are transferred via the copper A center of subunit 2 and heme A of subunit 1 to the bimetallic center formed by heme A3 and copper B. Publication Abstract from PubMedMammalian cytochrome c oxidase (CcO) reduces O(2) to water in a bimetallic site including Fe(a3) and Cu(B) giving intermediate molecules, termed A-, P-, F-, O-, E-, and R-forms. From the P-form on, each reaction step is driven by single-electron donations from cytochrome c coupled with the pumping of a single proton through the H-pathway, a proton-conducting pathway composed of a hydrogen-bond network and a water channel. The proton-gradient formed is utilized for ATP production by F-ATPase. For elucidation of the proton pumping mechanism, crystal structural determination of these intermediate forms is necessary. Here we report X-ray crystallographic analysis at approximately 1.8 A resolution of fully reduced CcO crystals treated with O(2) for three different time periods. Our disentanglement of intermediate forms from crystals that were composed of multiple forms determined that these three crystallographic data sets contained approximately 45% of the O-form structure, approximately 45% of the E-form structure, and approximately 20% of an oxymyoglobin-type structure consistent with the A-form, respectively. The O- and E-forms exhibit an unusually long Cu(B)(2+)-OH(-) distance and Cu(B)(1+)-H(2)O structure keeping Fe(a3)(3+)-OH(-) state, respectively, suggesting that the O- and E-forms have high electron affinities that cause the O-->E and E-->R transitions to be essentially irreversible and thus enable tightly coupled proton pumping. The water channel of the H-pathway is closed in the O- and E-forms and partially open in the R-form. These structures, together with those of the recently reported P- and F-forms, indicate that closure of the H-pathway water channel avoids back-leaking of protons for facilitating the effective proton pumping. Critical roles of the Cu(B) site in efficient proton pumping as revealed by crystal structures of mammalian cytochrome c oxidase catalytic intermediates.,Shimada A, Hara F, Shinzawa-Itoh K, Kanehisa N, Yamashita E, Muramoto K, Tsukihara T, Yoshikawa S J Biol Chem. 2021 Sep;297(3):100967. doi: 10.1016/j.jbc.2021.100967. Epub 2021 , Jul 15. PMID:34274318[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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