By the same authors

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Structures of Alcohol Dehydrogenases from Ralstonia and Sphingobium spp. Reveal the Molecular Basis for Their Recognition of ‘Bulky–Bulky’ Ketones

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Published copy (DOI)

Author(s)

  • Henry Man
  • Kinga Kędziora
  • Justyna Kulig
  • Annika Frank
  • Iván Lavandera
  • Vicente Gotor-Fernández
  • Dörte Rother
  • Sam Hart
  • Johan P. Turkenburg
  • Gideon Grogan

Department/unit(s)

Publication details

JournalTOPICS IN CATALYSIS
DateE-pub ahead of print - 13 Nov 2013
DatePublished (current) - Mar 2014
Issue number5
Volume57
Number of pages10
Pages (from-to)356-365
Early online date13/11/13
Original languageEnglish

Abstract

Alcohol dehydrogenases (ADHs) are applied in industrial synthetic chemistry for the production of optically active secondary alcohols. However, the substrate spectrum of many ADHs is narrow, and few, for example, are suitable for the reduction of prochiral ketones in which the carbonyl group is bounded by two bulky and/or hydrophobic groups; so-called ‘bulky–bulky’ ketones. Recently two ADHs, RasADH from Ralstonia sp. DSM 6428, and SyADH from Sphingobium yanoikuyae DSM 6900, have been described, which are distinguished by their ability to accept bulky–bulky ketones as substrates. In order to examine the molecular basis of the recognition of these substrates the structures of the native and NADPH complex of RasADH, and the NADPH complex of SyADH have been determined and refined to resolutions of 1.5, 2.9 and 2.5 Å, respectively. The structures reveal hydrophobic active site tunnels near the surface of the enzymes that are well-suited to the recognition of large hydrophobic substrates, as determined by modelling of the bulky–bulky substrate n-pentyl phenyl ketone. The structures also reveal the bases for NADPH specificity and (S)-stereoselectivity in each of the biocatalysts for n-pentyl phenyl ketone and related substrates.

    Research areas

  • Alcohol dehydrogenase, Ketoreductase, NADPH, Oxidoreductase, Enzyme structure

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