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High resolution crystal structure of Clostridium propionicum β-alanyl-CoA:ammonia lyase, a new member of the “hot dog fold” protein superfamily

Authors

  • Andreas Heine,

    1. Institut für Pharmazeutische Chemie, Fachbereich Pharmazie, Philipps-Universität Marburg, Marburg, Germany
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  • Gloria Herrmann,

    1. Laboratorium für Mikrobiologie und Synmikro, Fachbereich Biologie, Philipps-Universität Marburg, Marburg, Germany
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  • Thorsten Selmer,

    1. Laboratorium für Mikrobiologie und Synmikro, Fachbereich Biologie, Philipps-Universität Marburg, Marburg, Germany
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  • Felix Terwesten,

    1. Institut für Pharmazeutische Chemie, Fachbereich Pharmazie, Philipps-Universität Marburg, Marburg, Germany
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  • Wolfgang Buckel,

    1. Laboratorium für Mikrobiologie und Synmikro, Fachbereich Biologie, Philipps-Universität Marburg, Marburg, Germany
    2. Max-Planck-Institut für terrestrische Mikrobiologie, Marburg, Germany
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  • Klaus Reuter

    Corresponding author
    1. Institut für Pharmazeutische Chemie, Fachbereich Pharmazie, Philipps-Universität Marburg, Marburg, Germany
    • Correspondence to: Klaus Reuter, Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35032 Marburg, Germany. E-mail: reuterk@staff.uni-marburg.de

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  • Thorsten Selmer's current address is FH Aachen, Heinrich-Mußmann-Straße 1, D-52428 Jülich, Germany

Abstract

Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 Å as well as in complex with CoA at a resolution of 1.59 Å. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called “hot dog fold” which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all “hot dog fold” proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041–2053. © 2014 Wiley Periodicals, Inc.

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