Redox equilibria in hydroxylamine oxidoreductase. Electrostatic control of electron redistribution in multielectron oxidative processes

Igor V. Kurnikov, Mark A Ratner, A. Andrew Pacheco

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We report results of continuum electrostatics calculations of the cofactor redox potentials, and of the titratable group pKa values, in hydroxylamine oxidoreductase (HAO). A picture of a sophisticated multicomponent control of electron flow in the protein emerged from the studies. First, we found that neighboring heme cofactors strongly interact electrostatically, with energies of 50-100 mV. Thus, cofactor redox potentials depend on the oxidation state of other cofactors, and cofactor redox potentials in the active (partially oxidized) enzyme differ substantially from the values obtained in electrochemical redox titration experiments. We found that, together, solvent-exposed heme 1 (having a large negative redox potential) and heme 2 (having a large positive redox potential) form a lock for electrons generated during the oxidation reaction The attachment of HAO's physiological electron transfer partner cytochrome c554 results in a positive shift in the redox potential of heme 1, and "opens the electron gate". Electrons generated as a result of hydroxylamine oxidation travel to heme 3 and heme 8, which have redox potentials close to 0 mV versus NHE (this result is in partial disagreement with an existing experimental redox potential assignment). The closeness of hemes 3 and 8 from different enzyme subunits allows redistribution of the four electrons generated as a result of hydroxylamine oxidation, among the three enzyme subunits. For the multielectron oxidation process to be maximally efficient, the redox potentials of the electron-accepting cofactors should be roughly equal, and electrostatic interactions between extra electrons on these cofactors should be minimal. The redox potential assignments presented in the paper satisfy this general rule.

Original languageEnglish
Pages (from-to)1856-1863
Number of pages8
JournalBiochemistry
Volume44
Issue number6
DOIs
Publication statusPublished - Feb 15 2005

Fingerprint

hydroxylamine dehydrogenase
Static Electricity
Oxidation-Reduction
Electrostatics
Electrons
Heme
Oxidation
Hydroxylamine
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Redox equilibria in hydroxylamine oxidoreductase. Electrostatic control of electron redistribution in multielectron oxidative processes. / Kurnikov, Igor V.; Ratner, Mark A; Pacheco, A. Andrew.

In: Biochemistry, Vol. 44, No. 6, 15.02.2005, p. 1856-1863.

Research output: Contribution to journalArticle

@article{37507f8957a24f1fa12ccabf0c1bc77f,
title = "Redox equilibria in hydroxylamine oxidoreductase. Electrostatic control of electron redistribution in multielectron oxidative processes",
abstract = "We report results of continuum electrostatics calculations of the cofactor redox potentials, and of the titratable group pKa values, in hydroxylamine oxidoreductase (HAO). A picture of a sophisticated multicomponent control of electron flow in the protein emerged from the studies. First, we found that neighboring heme cofactors strongly interact electrostatically, with energies of 50-100 mV. Thus, cofactor redox potentials depend on the oxidation state of other cofactors, and cofactor redox potentials in the active (partially oxidized) enzyme differ substantially from the values obtained in electrochemical redox titration experiments. We found that, together, solvent-exposed heme 1 (having a large negative redox potential) and heme 2 (having a large positive redox potential) form a lock for electrons generated during the oxidation reaction The attachment of HAO's physiological electron transfer partner cytochrome c554 results in a positive shift in the redox potential of heme 1, and {"}opens the electron gate{"}. Electrons generated as a result of hydroxylamine oxidation travel to heme 3 and heme 8, which have redox potentials close to 0 mV versus NHE (this result is in partial disagreement with an existing experimental redox potential assignment). The closeness of hemes 3 and 8 from different enzyme subunits allows redistribution of the four electrons generated as a result of hydroxylamine oxidation, among the three enzyme subunits. For the multielectron oxidation process to be maximally efficient, the redox potentials of the electron-accepting cofactors should be roughly equal, and electrostatic interactions between extra electrons on these cofactors should be minimal. The redox potential assignments presented in the paper satisfy this general rule.",
author = "Kurnikov, {Igor V.} and Ratner, {Mark A} and Pacheco, {A. Andrew}",
year = "2005",
month = "2",
day = "15",
doi = "10.1021/bi048060v",
language = "English",
volume = "44",
pages = "1856--1863",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Redox equilibria in hydroxylamine oxidoreductase. Electrostatic control of electron redistribution in multielectron oxidative processes

AU - Kurnikov, Igor V.

AU - Ratner, Mark A

AU - Pacheco, A. Andrew

PY - 2005/2/15

Y1 - 2005/2/15

N2 - We report results of continuum electrostatics calculations of the cofactor redox potentials, and of the titratable group pKa values, in hydroxylamine oxidoreductase (HAO). A picture of a sophisticated multicomponent control of electron flow in the protein emerged from the studies. First, we found that neighboring heme cofactors strongly interact electrostatically, with energies of 50-100 mV. Thus, cofactor redox potentials depend on the oxidation state of other cofactors, and cofactor redox potentials in the active (partially oxidized) enzyme differ substantially from the values obtained in electrochemical redox titration experiments. We found that, together, solvent-exposed heme 1 (having a large negative redox potential) and heme 2 (having a large positive redox potential) form a lock for electrons generated during the oxidation reaction The attachment of HAO's physiological electron transfer partner cytochrome c554 results in a positive shift in the redox potential of heme 1, and "opens the electron gate". Electrons generated as a result of hydroxylamine oxidation travel to heme 3 and heme 8, which have redox potentials close to 0 mV versus NHE (this result is in partial disagreement with an existing experimental redox potential assignment). The closeness of hemes 3 and 8 from different enzyme subunits allows redistribution of the four electrons generated as a result of hydroxylamine oxidation, among the three enzyme subunits. For the multielectron oxidation process to be maximally efficient, the redox potentials of the electron-accepting cofactors should be roughly equal, and electrostatic interactions between extra electrons on these cofactors should be minimal. The redox potential assignments presented in the paper satisfy this general rule.

AB - We report results of continuum electrostatics calculations of the cofactor redox potentials, and of the titratable group pKa values, in hydroxylamine oxidoreductase (HAO). A picture of a sophisticated multicomponent control of electron flow in the protein emerged from the studies. First, we found that neighboring heme cofactors strongly interact electrostatically, with energies of 50-100 mV. Thus, cofactor redox potentials depend on the oxidation state of other cofactors, and cofactor redox potentials in the active (partially oxidized) enzyme differ substantially from the values obtained in electrochemical redox titration experiments. We found that, together, solvent-exposed heme 1 (having a large negative redox potential) and heme 2 (having a large positive redox potential) form a lock for electrons generated during the oxidation reaction The attachment of HAO's physiological electron transfer partner cytochrome c554 results in a positive shift in the redox potential of heme 1, and "opens the electron gate". Electrons generated as a result of hydroxylamine oxidation travel to heme 3 and heme 8, which have redox potentials close to 0 mV versus NHE (this result is in partial disagreement with an existing experimental redox potential assignment). The closeness of hemes 3 and 8 from different enzyme subunits allows redistribution of the four electrons generated as a result of hydroxylamine oxidation, among the three enzyme subunits. For the multielectron oxidation process to be maximally efficient, the redox potentials of the electron-accepting cofactors should be roughly equal, and electrostatic interactions between extra electrons on these cofactors should be minimal. The redox potential assignments presented in the paper satisfy this general rule.

UR - http://www.scopus.com/inward/record.url?scp=13644249873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13644249873&partnerID=8YFLogxK

U2 - 10.1021/bi048060v

DO - 10.1021/bi048060v

M3 - Article

C2 - 15697211

AN - SCOPUS:13644249873

VL - 44

SP - 1856

EP - 1863

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 6

ER -