Structural highlights
FunctionPublication Abstract from PubMedOne of the main factors hampering the implementation in industry of transaminase-based processes for the synthesis of enantiopure amines is their often low storage and operational stability. Our still limited understanding of the inactivation processes undermining the stability of wild-type transaminases represents an obstacle to improving their stability through enzyme engineering. In this paper we present a model describing the inactivation process of the well-characterized (S)-selective amine transaminase from Chromobacterium violaceum. The cornerstone of the model, supported by structural, computational, mutagenesis and biophysical data, is the central role of the catalytic lysine as a conformational switch. Upon breakage of the lysine-PLP Schiff base, the strain associated with the catalytically active lysine conformation is dissipated in a slow relaxation process capable of triggering the known structural rearrangements occurring in the holo-to-apo transition and ultimately promoting dimer dissociation. Due to the occurrence in the literature of similar PLP-dependent inactivation models valid for other non-transaminase enzymes belonging to the same fold-class, the role of the catalytic lysine as conformational switch might extend beyond the transaminase enzyme group and offer new insight to drive future non-trivial engineering strategies. Insight into the dimer dissociation process of the Chromobacterium violaceum (S)-selective amine transaminase.,Ruggieri F, Campillo-Brocal JC, Chen S, Humble MS, Walse B, Logan DT, Berglund P Sci Rep. 2019 Nov 18;9(1):16946. doi: 10.1038/s41598-019-53177-3. PMID:31740704[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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