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The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process.

Abstract：

:Mitochondrial cytochrome c oxidase plays an essential role in aerobic cellular respiration, reducing dioxygen to water in a process coupled with the pumping of protons across the mitochondrial inner membrane. An aspartate residue, Asp-51, located near the enzyme surface, undergoes a redox-coupled x-ray structural change, which is suggestive of a role for this residue in redox-driven proton pumping. However, functional or mechanistic evidence for the involvement of this residue in proton pumping has not yet been obtained. We report that the Asp-51 --> Asn mutation of the bovine enzyme abolishes its proton-pumping function without impairment of the dioxygen reduction activity. Improved x-ray structures (at 1.8/1.9-A resolution in the fully oxidized/reduced states) show that the net positive charge created upon oxidation of the low-spin heme of the enzyme drives the active proton transport from the interior of the mitochondria to Asp-51 across the enzyme via a water channel and a hydrogen-bond network, located in tandem, and that the enzyme reduction induces proton ejection from the aspartate to the mitochondrial exterior. A peptide bond in the hydrogen-bond network critically inhibits reverse proton transfer through the network. A redox-coupled change in the capacity of the water channel, induced by the hydroxyfarnesylethyl group of the low-spin heme, suggests that the channel functions as an effective proton-collecting region. Infrared results indicate that the conformation of Asp-51 is controlled only by the oxidation state of the low-spin heme. These results indicate that the low-spin heme drives the proton-pumping process.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Tsukihara T,Shimokata K,Katayama Y,Shimada H,Muramoto K,Aoyama H,Mochizuki M,Shinzawa-Itoh K,Yamashita E,Yao M,Ishimura Y,Yoshikawa S

doi

10.1073/pnas.2635097100

keywords:

subject

Has Abstract

pub_date

2003-12-23 00:00:00

pages

15304-9

issue

eissn

0027-8424

issn

1091-6490

pii

2635097100

journal_volume

100

pub_type

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The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process.