Dataset Information

Structure of the cytochrome aa ₃ -600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site.

ABSTRACT: Virtually all proton-pumping terminal respiratory oxygen reductases are members of the heme-copper oxidoreductase superfamily. Most of these enzymes use reduced cytochrome c as a source of electrons, but a group of enzymes have evolved to directly oxidize membrane-bound quinols, usually menaquinol or ubiquinol. All of the quinol oxidases have an additional transmembrane helix (TM0) in subunit I that is not present in the related cytochrome c oxidases. The current work reports the 3.6-Å-resolution X-ray structure of the cytochrome aa ₃ -600 menaquinol oxidase from Bacillus subtilis containing 1 equivalent of menaquinone. The structure shows that TM0 forms part of a cleft to accommodate the menaquinol-7 substrate. Crystals which have been soaked with the quinol-analog inhibitor HQNO (N-oxo-2-heptyl-4-hydroxyquinoline) or 3-iodo-HQNO reveal a single binding site where the inhibitor forms hydrogen bonds to amino acid residues shown previously by spectroscopic methods to interact with the semiquinone state of menaquinone, a catalytic intermediate.

SUBMITTER: Xu J

PROVIDER: S-EPMC6969530 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Structure of the cytochrome aa3 -600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site.

Xu Jingjing J Ding Ziqiao Z Liu Bing B Yi Sophia M SM Li Jiao J Zhang Zhengguang Z Liu Yuchen Y Li Jin J Liu Liu L Zhou Aiwu A Zhou Aiwu A Gennis Robert B RB Zhu Jiapeng J

Proceedings of the National Academy of Sciences of the United States of America 20191230 2

Virtually all proton-pumping terminal respiratory oxygen reductases are members of the heme-copper oxidoreductase superfamily. Most of these enzymes use reduced cytochrome c as a source of electrons, but a group of enzymes have evolved to directly oxidize membrane-bound quinols, usually menaquinol or ubiquinol. All of the quinol oxidases have an additional transmembrane helix (TM0) in subunit I that is not present in the related cytochrome c oxidases. The current work reports the 3 ...[more]

PMID: 31888984

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Project description:Staphylococcus aureus is the leading cause of skin and soft tissue infections, bacteremia, osteomyelitis, and endocarditis in the developed world. The ability of S. aureus to cause substantial disease in distinct host environments is supported by a flexible metabolism that allows this pathogen to overcome challenges unique to each host organ. One feature of staphylococcal metabolic flexibility is a branched aerobic respiratory chain composed of multiple terminal oxidases. Whereas previous biochemical and spectroscopic studies reported the presence of three different respiratory oxygen reductases (o type, bd type, and aa3 type), the genome contains genes encoding only two respiratory oxygen reductases, cydAB and qoxABCD Previous investigation showed that cydAB and qoxABCD are required to colonize specific host organs, the murine heart and liver, respectively. This work seeks to clarify the relationship between the genetic studies showing the unique roles of the cydAB and qoxABCD in virulence and the respiratory reductases reported in the literature. We establish that QoxABCD is an aa3-type menaquinol oxidase but that this enzyme is promiscuous in that it can assemble as a bo3-type menaquinol oxidase. However, the bo3 form of QoxABCD restricts the carbon sources that can support the growth of S. aureus In addition, QoxABCD function is supported by a previously uncharacterized protein, which we have named CtaM, that is conserved in aerobically respiring Firmicutes In total, these studies establish the heme A biosynthesis pathway in S. aureus, determine that QoxABCD is a type aa3 menaquinol oxidase, and reveal CtaM as a new protein required for type aa3 menaquinol oxidase function in multiple bacterial genera. Staphylococcus aureus relies upon the function of two terminal oxidases, CydAB and QoxABCD, to aerobically respire and colonize distinct host tissues. Previous biochemical studies support the conclusion that a third terminal oxidase is also present. We establish the components of the S. aureus electron transport chain by determining the heme cofactors that interact with QoxABCD. This insight explains previous observations by revealing that QoxABCD can utilize different heme cofactors and confirms that the electron transport chain of S. aureus is comprised of two terminal menaquinol oxidases. In addition, a newly identified protein, CtaM, is found to be required for the function of QoxABCD. These results provide a more complete assessment of the molecular mechanisms that support staphylococcal respiration.

Dataset Information

Structure of the cytochrome aa ₃ -600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site.

Publications

Structure of the cytochrome <i>aa</i><sub><i>3</i></sub> -600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site.

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Dataset Information

Structure of the cytochrome aa 3 -600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site.

Publications

Structure of the cytochrome <i>aa</i><sub><i>3</i></sub> -600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Structure of the cytochrome aa ₃ -600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site.