Structural studies of Pseudomonas and Chromobacteriumω‐aminotransferases provide insights into their differing substrate specificity. (24th March 2013)

• Record Type: Journal Article
• Authors: Sayer, Christopher; Isupov, Michail N.; Westlake, Aaron; Littlechild, Jennifer A.
• Is Part Of: Acta crystallographica. Volume 69:Part 4(2013:Apr.)
• Page Start: 564
• Page End: 576
• Publication Date: 2013-03-24
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S0907444912051670
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The crystal structures and inhibitor complexes of two industrially important ω‐aminotransferase enzymes from <italic>Pseudomonas aeruginosa</italic> and <italic>Chromobacterium violaceum</italic> have been determined in order to understand the differences in their substrate specificity. The two enzymes share 30% sequence identity and use the same amino acceptor, pyruvate; however, the <italic>Pseudomonas</italic> enzyme shows activity towards the amino donor β‐alanine, whilst the <italic>Chromobacterium</italic> enzyme does not. Both enzymes show activity towards <italic>S</italic>‐α‐methylbenzylamine (MBA), with the <italic>Chromobacterium</italic> enzyme having a broader substrate range. The crystal structure of the <italic>P. aeruginosa</italic> enzyme has been solved in the holo form and with the inhibitor gabaculine bound. The <italic>C. violaceum</italic> enzyme has been solved in the apo and holo forms and with gabaculine bound. The structures of the holo forms of both enzymes are quite similar. There is little conformational difference observed between the inhibitor complex and the holoenzyme for the <italic>P. aeruginosa</italic> aminotransferase. In comparison, the crystal structure of the <italic>C. violaceum</italic> gabaculine complex shows significant structural rearrangements from the structures of both the apo and holo forms of the enzyme. It appears that the different rigidity of the protein scaffold contributes to the substrate specificity observed for the two ω‐aminotransferases.</p> </abstract>