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Structural Characterization of an S-enantioselective Imine Reductase from Mycobacterium Smegmatis.

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Meyer T, Zumbrägel N, Geerds C, Gröger H, Niemann HH
OpenAccess logo Biomolecules 10 (2020)
Cited: 5 times
EuropePMC logo PMID: 32751900

Abstract

NADPH-dependent imine reductases (IREDs) are enzymes capable of enantioselectively reducing imines to chiral secondary amines, which represent important building blocks in the chemical and pharmaceutical industry. Since their discovery in 2011, many previously unknown IREDs have been identified, biochemically and structurally characterized and categorized into families. However, the catalytic mechanism and guiding principles for substrate specificity and stereoselectivity remain disputed. Herein, we describe the crystal structure of S-IRED-Ms from Mycobacterium smegmatis together with its cofactor NADPH. S-IRED-Ms belongs to the S-enantioselective superfamily 3 (SFam3) and is the first IRED from SFam3 to be structurally described. The data presented provide further evidence for the overall high degree of structural conservation between different IREDs of various superfamilies. We discuss the role of Asp170 in catalysis and the importance of hydrophobic amino acids in the active site for stereospecificity. Moreover, a separate entrance to the active site, potentially functioning according to a gatekeeping mechanism regulating access and, therefore, substrate specificity is described.

Articles - 6smt mentioned but not cited (1)

  1. Structural Characterization of an S-enantioselective Imine Reductase from Mycobacterium Smegmatis. Meyer T, Zumbrägel N, Geerds C, Gröger H, Niemann HH. Biomolecules 10 E1130 (2020)


Articles citing this publication (4)

  1. Computational Study of Mechanism and Enantioselectivity of Imine Reductase from Amycolatopsis orientalis. Prejanò M, Sheng X, Himo F. ChemistryOpen 11 e202100250 (2022)
  2. Inverting the Stereoselectivity of an NADH-Dependent Imine-Reductase Variant. Stockinger P, Borlinghaus N, Sharma M, Aberle B, Grogan G, Pleiss J, Nestl BM. ChemCatChem 13 5210-5215 (2021)
  3. Conformational changes of loops highlight a potential binding site in Rhodococcus equi VapB. Geerds C, Haas A, Niemann HH. Acta Crystallogr F Struct Biol Commun 77 246-253 (2021)
  4. Actinomycetes-derived imine reductases with a preference towards bulky amine substrates. Zhang J, Li X, Chen R, Tan X, Liu X, Ma Y, Zhu F, An C, Wei G, Yao Y, Yang L, Zhang P, Wu Q, Sun Z, Wang BG, Gao SS, Cui C. Commun Chem 5 123 (2022)


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