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Oxalate decarboxylase uses electron hole hopping for catalysis.

Publication ,  Journal Article
Pastore, AJ; Teo, RD; Montoya, A; Burg, MJ; Twahir, UT; Bruner, SD; Beratan, DN; Angerhofer, A
Published in: The Journal of biological chemistry
July 2021

The hexameric low-pH stress response enzyme oxalate decarboxylase catalyzes the decarboxylation of the oxalate mono-anion in the soil bacterium Bacillus subtilis. A single protein subunit contains two Mn-binding cupin domains, and catalysis depends on Mn(III) at the N-terminal site. The present study suggests a mechanistic function for the C-terminal Mn as an electron hole donor for the N-terminal Mn. The resulting spatial separation of the radical intermediates directs the chemistry toward decarboxylation of the substrate. A π-stacked tryptophan pair (W96/W274) links two neighboring protein subunits together, thus reducing the Mn-to-Mn distance from 25.9 Å (intrasubunit) to 21.5 Å (intersubunit). Here, we used theoretical analysis of electron hole-hopping paths through redox-active sites in the enzyme combined with site-directed mutagenesis and X-ray crystallography to demonstrate that this tryptophan pair supports effective electron hole hopping between the C-terminal Mn of one subunit and the N-terminal Mn of the other subunit through two short hops of ∼8.5 Å. Replacement of W96, W274, or both with phenylalanine led to a large reduction in catalytic efficiency, whereas replacement with tyrosine led to recovery of most of this activity. W96F and W96Y mutants share the wildtype tertiary structure. Two additional hole-hopping networks were identified leading from the Mn ions to the protein surface, potentially protecting the enzyme from high Mn oxidation states during turnover. Our findings strongly suggest that multistep hole-hopping transport between the two Mn ions is required for enzymatic function, adding to the growing examples of proteins that employ aromatic residues as hopping stations.

Duke Scholars

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

July 2021

Volume

297

Issue

1

Start / End Page

100857

Related Subject Headings

  • Tryptophan
  • Oxygen
  • Manganese
  • Kinetics
  • Electrons
  • Crystallography, X-Ray
  • Catalytic Domain
  • Catalysis
  • Carboxy-Lyases
  • Biochemistry & Molecular Biology
 

Citation

APA
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ICMJE
MLA
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Pastore, A. J., Teo, R. D., Montoya, A., Burg, M. J., Twahir, U. T., Bruner, S. D., … Angerhofer, A. (2021). Oxalate decarboxylase uses electron hole hopping for catalysis. The Journal of Biological Chemistry, 297(1), 100857. https://doi.org/10.1016/j.jbc.2021.100857
Pastore, Anthony J., Ruijie D. Teo, Alvaro Montoya, Matthew J. Burg, Umar T. Twahir, Steven D. Bruner, David N. Beratan, and Alexander Angerhofer. “Oxalate decarboxylase uses electron hole hopping for catalysis.The Journal of Biological Chemistry 297, no. 1 (July 2021): 100857. https://doi.org/10.1016/j.jbc.2021.100857.
Pastore AJ, Teo RD, Montoya A, Burg MJ, Twahir UT, Bruner SD, et al. Oxalate decarboxylase uses electron hole hopping for catalysis. The Journal of biological chemistry. 2021 Jul;297(1):100857.
Pastore, Anthony J., et al. “Oxalate decarboxylase uses electron hole hopping for catalysis.The Journal of Biological Chemistry, vol. 297, no. 1, July 2021, p. 100857. Epmc, doi:10.1016/j.jbc.2021.100857.
Pastore AJ, Teo RD, Montoya A, Burg MJ, Twahir UT, Bruner SD, Beratan DN, Angerhofer A. Oxalate decarboxylase uses electron hole hopping for catalysis. The Journal of biological chemistry. 2021 Jul;297(1):100857.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

July 2021

Volume

297

Issue

1

Start / End Page

100857

Related Subject Headings

  • Tryptophan
  • Oxygen
  • Manganese
  • Kinetics
  • Electrons
  • Crystallography, X-Ray
  • Catalytic Domain
  • Catalysis
  • Carboxy-Lyases
  • Biochemistry & Molecular Biology