Cited by 56Aldose Reductase and TaurineEnzyme Catalysis and ImmobilizationEnzyme Structure and Function

Catalytic mechanism and substrate selectivity of aldo-keto reductases: Insights from structure-function studies of Candida tenuis xylose reductase

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Kratzer, Regina, Wilson, David, Nidetzky, Bernd·2006·IUBMB Life (International Union of Biochemistry and Molecular Biology: Life)

Abstract

Aldo-keto reductases (AKRs) constitute a large protein superfamily of mainly NAD(P)-dependent oxidoreductases involved in carbonyl metabolism. Catalysis is promoted by a conserved tetrad of active site residues (Tyr, Lys, Asp and His). Recent results of structure-function relationship studies for xylose reductase (AKR2B5) require an update of the proposed catalytic mechanism. Electrostatic stabilization by the epsilon-NH3+ group of Lys is a key source of catalytic power of xylose reductase. A molecular-level analysis of the substrate binding pocket of xylose reductase provides a case of how a very broadly specific AKR achieves the requisite selectivity for its physiological substrate and could serve as the basis for the design of novel reductases with improved specificities for biocatalytic applications.

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  • AKR catalytic mechanism is similar to that of SDRs, using an active-site Tyr and an assisting Lys to deprotonate the Tyr hydroxyl.

    “The catalytic mechanism of AKR’s, in principle, is similar to that found in SDR’s with an active site Tyr residue and an assisting Lys residue facilitating the deprotonation of the Tyr hydroxyl group.384”

    From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [384]

    The Acid/base Catalysis—Tyr-51 section identifies an active-site Tyr as the likely catalytic acid. But it says that, in AKR2B5, interaction with Lys-80 is not required to lower Tyr-51’s pKa; the Electrostatic stabilization—Lys-80 section instead proposes an electrostatic role for Lys. The cited passages do not establish the stated comparison with SDRs. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Research works printed but not linked: 1

  1. Kratzer, R., and Nidetzky, B. (2006) Structure-function relationships for Candida tenuis xylose reductase (AKR2B5): properties of H113E mutant. In Enzymology and Molecular Biology of Carbonyl Metabolism-12 (Weiner H., Plapp B., Lindahl, R., and Maser E. eds.). pp. 404 -412, Purdue University Press, West Lafayette, Indiana.

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Authors
Kratzer, R., Wilson, D., & Nidetzky, B.
Affiliations
  • Graz University of Technology (AT)
  • University of California, Davis (US)
Venue
IUBMB Life (International Union of Biochemistry and Molecular Biology: Life)
Publisher
Wiley
Published
2006-09-01
Volume
58
Issue
9
Pages
499-507
ISSN
  • 1521-6543 (ISSN-L)
  • 1521-6551
OpenAlex
W2085321839
Cited by
56
References
45
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 9 · 2019: 5 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 2
FWCI
0.13
Type
journal article
Language
en
Open access
Locations
  • IUBMB Life (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • W. M. Keck Foundation
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
aldo-keto reductase, xylose reductase, Candida tenuis, catalytic mechanism, substrate specificity, structure-function relationship, electrostatic stabilization, active site residues, substrate binding pocket, biocatalyst design
MeSH terms
Aldo-Keto Reductases, Alcohol Oxidoreductases, Aldehyde Reductase, Candida, Catalysis, Fungal Proteins, Models, Chemical, Models, Molecular, Protein Binding, Structure-Activity Relationship, Substrate Specificity, Xylose, Crystallography, X-Ray, Static Electricity

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