Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase.

Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase. Research Abstract Details 

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Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase. Abstract Text:

Jinyou Zhuang,Jennifer H Amoroso,Ryan Kinloch,John H Dawson,Michael J Baldwin,Brian R Gibney,

Heme a, the metalloporphyrin cofactor unique to cytochrome c oxidases, differs from the more common heme b by two chemical modifications, a C-2 hydroxyethylfarnesyl group and a C-8 formyl group. To elucidate a role of the C-8 formyl group, we compare the heme affinity, spectroscopy, and electrochemistry of a heme a mimic, Fe(diacetyldeuterioporphyrin IX) or Fe(DADPIX), with heme b, Fe(protoporphryrin IX) or Fe(PPIX), incorporated into a designed heme protein. The [Delta7-H3m]2 protein ligand, or maquette, selected for this study contains two equivalent bis-(3-methyl-L-histidine) heme binding sites within a four-alpha-helix bundle scaffold. The spectroscopic data on Fe(PPIX) and Fe(DADPIX) bound to [Delta7-H3m]2 demonstrate that these complexes are excellent synthetic analogues for natural cytochromes b and a, respectively. Comparison of the spectroscopic, electrochemical, and equilibrium thermodynamic data measured for the Fe(PPIX)-[Delta7-H3m]2 maquette with the previously reported Fe(PPIX)-[Delta7-His]2 complex demonstrates that changing the heme axial ligands to 3-methyl-L-histidine from L-histidine does not alter the resulting heme protein properties significantly in either oxidation state. Heme binding studies demonstrate that [Delta7-H3m]2 binds two ferrous Fe(DADPIX) or Fe(PPIX) moieties with similar dissociation constant values. However, in the ferric state, the data show that [Delta7-H3m]2 only binds a single Fe(DADPIX) and that one 2500-fold weaker than oxidized Fe(PPIX). The data demonstrate that the 4.6 kcal mol(-1) weakened affinity of [Delta7-H3m]2 for oxidized Fe(DADPIX) results in the majority of the 160 mV, 3.7 kcal mol(-1), positive shift in the heme reduction potential relative to Fe(PPIX). These data indicate that a role of the formyl group on heme a is to raise the iron reduction potential, thus making it a better electron acceptor, but that it does so by destabilizing the affinity of bis-imidazole sites for the ferric state.

Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase. Publishing Authors By Initials

J Zhuang,JH Amoroso,R Kinloch,JH Dawson,MJ Baldwin,BR Gibney,

For similar investigative techniques: chemistry, analytical: scattering, radiation: spectrum analysis, raman research abstracts see: investigative techniques: chemistry, analytical: scattering, radiation: spectrum analysis, raman research

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Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Inorganic chemistry

VOLUME: 45

Page Numbers: 4685-94

Journal Abbreviation:

ISSN: 0020-1669

DAY: 12

MONTH: Jun

YEAR: 2006

Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 366543

Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase. Keywords Mesh Terms:

KEYWORDS: Spectrum Analysis, Raman

MESH TERMS: chemistry

Chemical & Substance for Abstract: Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase. Information

Substance Name: Electron Transport Complex IV

Registry Number: EC 1.9.3.1

Grant and Affiliation Information for Evaluation of electron-withdrawing group effects on heme binding in designed proteins: implications for heme a in cytochrome c oxidase.

AFFILIATION: Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: T32 GM 08281

ACRONYM: GM

MEDLINETA: Inorg Chem

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