6s4g
From Proteopedia
Crystal structure of the omega transaminase from Chromobacterium violaceum in complex with PMP
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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