3wwj

Crystal structure of an engineered sitagliptin-producing transaminase, ATA-117-Rd11

spinqualitylabelsall models 3wwj, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wwj is a 12 chain structure with sequence from Arthrobacter sp. KNK168. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: CSO, PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F7J696_9MICC Publication Abstract from PubMed (R)-stereospecific amine transaminases (R-ATAs) are important biocatalysts for the production of (R)-amine compounds in a strict stereospecific manner. An improved R-ATA, ATA-117-Rd11, was successfully engineered for the manufacture of sitagliptin, a widely used therapeutic agent for type-2 diabetes. The effects of the individual mutations, however, have not yet been demonstrated due to the lack of experimentally determined structural information. Here we describe three crystal structures of the first isolated R-ATA, its G136F mutant and engineered ATA-117-Rd11, which indicated that the mutation introduced into the 136(th) residue altered the conformation of a loop next to the active site, resulting in a substrate-binding site with drastically modified volume, shape, and surface properties, to accommodate the large pro-sitagliptin ketone. Our findings provide a detailed explanation of the previously reported molecular engineering of ATA-117-Rd11 and propose that the loop near the active site is a new target for the rational design to change the substrate specificity of ATAs. A new target region for changing the substrate specificity of amine transaminases.,Guan LJ, Ohtsuka J, Okai M, Miyakawa T, Mase T, Zhi Y, Hou F, Ito N, Iwasaki A, Yasohara Y, Tanokura M Sci Rep. 2015 Jun 1;5:10753. doi: 10.1038/srep10753. PMID:26030619 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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