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      Insights into the Biosynthesis of the Vibrio cholerae Major Autoinducer CAI-1 from the Crystal Structure of the PLP-Dependent Enzyme CqsA

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          Abstract

          CqsA is an enzyme involved in the biosynthesis of cholerae autoinducer-1 (CAI-1), the major Vibrio cholerae autoinducer engaged in quorum sensing. The amino acid sequence of CqsA suggests that it belongs to the family of alpha-oxoamine synthases that catalyse the condensation of an amino acid to an acyl-CoA substrate. Here we present the apo- and PLP-bound crystal structures of CqsA and confirm that it shares structural homology with the dimeric alpha-oxoamine synthases, including a conserved PLP-binding site. The chemical structure of CAI-1 suggests that decanoyl-CoA may be one substrate of CqsA and that another substrate may be l-threonine or l-2-aminobutyric acid. A crystal structure of CqsA at 1.9-A resolution obtained in the presence of PLP and l-threonine reveals an external aldimine that has lost the l-threonine side chain. Similarly, a 1.9-A-resolution crystal structure of CqsA in the presence of PLP, l-threonine, and decanoyl-CoA shows a trapped external aldimine intermediate, suggesting that the condensation and decarboxylation steps have occurred, again with loss of the l-threonine side chain. It is suggested that this side-chain loss, an observation supported by mass spectrometry, is due to a retro-aldol reaction. Although no structural data have been obtained on CqsA using l-2-aminobutyric acid and decanoyl-CoA as substrates, mass spectrometry confirms the expected product of the enzyme reaction. It is proposed that a region of structure that is disordered in the apo structure is involved in the release of product. While not confirming if CqsA alone is able to synthesize CAI-1, these results suggest possible synthetic routes.

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          Author and article information

          Journal
          Journal of Molecular Biology
          Journal of Molecular Biology
          Elsevier BV
          00222836
          September 2009
          September 2009
          : 392
          : 3
          : 763-773
          Article
          10.1016/j.jmb.2009.07.042
          19631226
          7f5cf6e5-6adb-4fb3-93b5-86d21a9ed14d
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/


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