Nihon Kessho Gakkaishi
Online ISSN : 1884-5576
Print ISSN : 0369-4585
ISSN-L : 0369-4585
Review Articles
Investigation of Enzyme Reaction Mechanism, and Exploration and Construction of New Enzymes Based on Crystal Structures
Masahiro FUJIHASHI
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2024 Volume 66 Issue 2 Pages 87-93

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Abstract

Enzymes are tremendous catalysts. Protein crystallography widely and deeply contributes to the elucidation of their reaction mechanism as well as to the exploration and modification of useful enzymes. Structure analysis of orotidine monophosphate decarboxylase(ODCase), which is one of the most proficient enzymes, also elucidates its reaction mechanism, in which the substrate distortion largely contributes to the catalysis. The distortion destabilizes the enzyme-substrate complex but not the transition state complex, to increase both kcat/KM and kcat along with transition state stabilization. Besides, this review focuses on the pyrophosphate dependent kinases(PPi-kinases)as an example of the exploration and modification of useful enzymes. Kinases typically transfer a phosphate group from a nucleoside triphosphate such as ATP to a suitable acceptor molecule, but rarely utilize pyrophosphate as a phosphate donor. We have identified several PPi-kinases based on the structural features elucidated by crystallographic analysis. Crystallographic data also enabled us to alter the product of a PPi-kinase by replacing the ligand recognition residues. The combination of crystallography-based methodology with AlphaFold2/AlphaFold3 prediction promises further discovery of novel enzymes and the alternation of the enzymatic reactions.

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© The Crystallographic Society of Japan
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