Inhibitory effects of a novel Val to Thr mutation on the distal heme of human catalase.

Mashhadi Z, Boeglin WE, Brash AR
Biochimie. 2014 106: 180-3

PMID: 25086217 · PMCID: PMC4250446 · DOI:10.1016/j.biochi.2014.07.021

True catalases efficiently breakdown hydrogen peroxide, whereas the catalase-related enzyme allene oxide synthase (cAOS) is completely unreactive and instead metabolizes a fatty acid hydroperoxide. In cAOS a Thr residue adjacent to the distal His restrains reaction with H2O2 (Tosha et al. (2006) J. Biol. Chem. 281:12610; De Luna et al. (2013) J. Phys. Chem. B 117: 14635) and its mutation to the consensus Val of true catalases permits the interaction. Here we investigated the effects of the reciprocal experiment in which the Val74 of human catalase is mutated to Thr, Ser, Met, Pro, or Ala. The Val74Thr substitution decreased catalatic activity by 3.5-fold and peroxidatic activity by 3-fold. Substitution with Ser had similar negative effects (5- and 3-fold decreases). Met decreased catalatic activity 2-fold and eliminated peroxidatic activity altogether, whereas the Val74Ala substitution was well tolerated. (The Val74Pro protein lacked heme). We conclude that the conserved Val74 of true catalases helps optimize catalysis. There are rare substitutions of Val74 with Ala, Met, or Pro, but not with Ser of Thr, possibly due their hydrogen bonding affecting the conformation of His75, the essential distal heme residue for activity in catalases.

Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

MeSH Terms (18)

Amino Acid Sequence Biocatalysis Catalase Catalytic Domain Crystallography, X-Ray Heme Humans Hydrogen Bonding Hydrogen Peroxide Models, Molecular Molecular Structure Mutant Proteins Mutation, Missense Peroxides Protein Structure, Tertiary Sequence Homology, Amino Acid Threonine Valine

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