Anesthetic-like Interactions of Nitric Oxide with Albumin and Hemeproteins: A MECHANISM FOR CONTROL OF PROTEIN FUNCTION

Vijaya Sampath,Xiao-Jian Zhao,Winslow S Caughey

doi:10.1074/jbc.m006588200

Vijaya Sampath, Xiao-Jian Zhao + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m006588200

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Abstract

Noncovalent bonding interactions of nitric oxide (NO) with human serum albumin (HSA), human hemoglobin A, bovine myoglobin, and bovine cytochrome c oxidase (CcO) have been explored. The anesthetic nitrous oxide (NNO) occupies multiple sites within each protein, but does not bind to heme iron. Infrared (IR) spectra of NNO molecules sequestered within albumin, with NO present, support the binding of NO and NNO to the same sites with comparable affinities. Perturbations of IR spectra of the Cys(34) thiol of HSA indicate NO, NNO, halothane, and chloroform can induce similar changes in protein structure. Experiments evaluating the relative affinities of binding of NO and carbon monoxide (CO) to iron(II) sites of the hemeproteins led to evidence of NO binding to noniron, nonsulfur sites as well. With HbA, IR spectra of cysteine thiols and/or the iron(II) N-O stretching region denote changes in protein structure due to NO, NNO, or CO occupying noniron sites with an order of decreasing affinities of NO > NNO > CO. Loss of NO from some, not all, noniron sites in hemeproteins is very slow (t(1/2) approximately hours). These findings provide examples in which NO and anesthetics alter the structure and properties of protein similarly, and support the hypothesis that some physiological effects of NO (and possibly CO) result from anesthetic-like noncovalent bonding to sites within protein or other tissue components. Such bonding may be involved in mechanisms for control of oxygen transport, mitochondrial respiration, and activation of soluble guanylate cyclase by NO.

Highlights

From the ‡Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523 and the ʈLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840
The number of “slow release” noniron sites approximates the number of NNO sites estimated earlier [5], a finding consistent with, but not proof of, nitric oxide (NO) and NNO binding at the same sites
The ability of aromatic ring structures to bind NO, tightly and reversibly, is shown unequivocally by the NO binding between the cofacial aromatic groups of so-called “Venus fly trap” organic compounds recently reported by Kochi and co-workers [45, 46]

Summary

Introduction

From the ‡Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523 and the ʈLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840. Loss of NO from some, not all, noniron sites in hemeproteins is very slow (t1⁄2 ϳ hours) These findings provide examples in which NO and anesthetics alter the structure and properties of protein and support the hypothesis that some physiological effects of NO (and possibly CO) result from anesthetic-like noncovalent bonding to sites within protein or other tissue components. Such bonding may be involved in mechanisms for control of oxygen transport, mitochondrial respiration, and activation of soluble guanylate cyclase by NO.

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