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ATP binding to cytochrome c diminishes electron flow in the mitochondrial respiratory pathway
Author(s) -
Craig Douglas B.,
Wallace CARMICHAEL J. A.
Publication year - 1993
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560020610
Subject(s) - adenosine triphosphate , oxidative phosphorylation , cytochrome c , electron transport chain , adduct , biochemistry , chemistry , mitochondrion , biophysics , binding site , stereochemistry , biology , organic chemistry
Eukaryotic cytochrome c possesses an ATP‐binding site of substantial specificity and high affinity that is conserved between highly divergent species and which includes the invariant residue arginine 91 . Such evolutionary conservatism strongly suggests a physiological role for ATP binding that demands further investigation. We report the preparation of adducts of the protein and the affinity labels 8‐azido adenosine 5′‐triphosphate, adenosine 5′‐triphosphate‐2′, 3′‐dialdehyde, and 5′‐ p ‐fluorosulfonylbenzoyladenosine. The two former reagents were seen to react at the arginine 91 ‐containing site, yet the reaction of the latter, although specific, occurred elsewhere, suggesting caution is necessary in its use. None of the adducts displayed significant modification of global structure, stability, or physicochemical properties, leading us to believe that the 8‐N 3 ‐ATP and oATP adducts are good stabilized models of the noncovalent interaction; yet modification led to significant, and sometimes pronounced, effects on biological activity. We therefore propose that the role of ATP binding to this site, which we have shown to occur when the phosphorylation potential of the system is high under the equivalent of physiological conditions, is to cause a decrease in electron flow through the mitochondrial electron transport chain. Differences in the degree of inhibition produced by differences in adduct chemistry suggest that this putative regulatory role is mediated primarily by electrostatic effects.

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