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Structure, redox, pK a, spin. A golden tetrad for understanding metalloenzyme energetics and reaction pathways

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Abstract

After a review of the current status of density functional theory (DFT) for spin-polarized and spin-coupled systems, we focus on the resting states and intermediates of redox-active metalloenzymes and electron transfer proteins, showing how comparisons of DFT-calculated spectroscopic parameters with experiment and evaluation of related energies and geometries provide important information. The topics we examine include (1) models for the active-site structure of methane monooxygenase intermediate Q and ribonucleotide reductase intermediate X; (2) the coupling of electron transfer to proton transfer in manganese superoxide dismutase, with implications for reaction kinetics; (3) redox, pK a, and electronic structure issues in the Rieske iron–sulfur protein, including their connection to coupled electron/proton transfer, and an analysis of how partial electron delocalization strongly alters the electron paramagnetic resonance spectrum; (4) the connection between protein-induced structural distortion and the electronic structure of oxidized high-potential 4Fe4S proteins with implications for cluster reactivity; (5) an analysis of cluster assembly and central-atom insertion into the FeMo cofactor center of nitrogenase based on DFT structural and redox potential calculations.

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Notes

  1. We warn the reader at this point that the terms “electron exchange”, or “electron exchange potential,” or “exchange hole” have different meanings in HF and DFT methods because these methods are constructed from different starting points. There is a fairly close correspondence for atoms, but not for molecules, and these differences are important.

Abbreviations

ADF:

Amsterdam Density Functional

BP:

Becke 1988–Perdew 1986

BS:

Broken symmetry

B86:

Becke 1986

B88:

Becke 1988

COSMO:

Conductor-like screening model

DFT:

Density functional theory

ENDOR:

Electron–nuclear double resonance

ESEEM:

Electron spin echo envelope modulation

EXAFS:

Extended X-ray absorption fine structure

GGA:

Generalized gradient approximation

G96:

Gill 1996

HF:

Hartree–Fock

HIPIP:

High-potential 4Fe4S protein

LSDA:

Local spin density approximation

MCD:

Magnetic circular dichroism

MM:

Molecular mechanics

MMOH:

Methane monooxygenase

PW91:

Perdew–Wang 1991

QM:

Quantum mechanics

RNR:

Ribonucleotide reductase

RSCP:

Resonance spin crossover pair

SCF:

Self-consistent field

SOD:

Superoxide dismutase

VWN:

Vosko–Wilk–Nusair

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Acknowledgements

We want to thank all the former group members who contributed to some of the research reported here, particularly T. Lovell, R. Torres, F. Himo, J. Li, T. Liu, G.M. Ullmann, L. Hunsicker-Wang, J.-M. Mouesca, C.L. Fisher, R. Konecny, X.-G. Zhao, S. Sinnecker, and my collaborators D.A. Case, J.A. Fee, and D. Bashford. We thank V. Roberts, J.A. Fee, and V. Pelmenschikov for their critical reading and comments on the manuscript. This work was funded by NIH grants GM43278 and GM39914.

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  1. Department of Molecular Biology, TPC15, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Louis Noodleman & Wen-Ge Han

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  1. Louis Noodleman
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Correspondence to Louis Noodleman.

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Noodleman, L., Han, WG. Structure, redox, pK a, spin. A golden tetrad for understanding metalloenzyme energetics and reaction pathways. J Biol Inorg Chem 11, 674–694 (2006). https://doi.org/10.1007/s00775-006-0136-3

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