8x3g

Crystal structure of metformin hydrolase from Aminobacter

spinqualitylabelsall models 8x3g, resolution 1.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8x3g is a 6 chain structure with sequence from Aminobacter sp. NyZ550. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.84Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The biguanide drug metformin is a first-line blood glucose-lowering medication for type 2 diabetes, leading to its presence in the global environment. However, little is known about the fate of metformin by microbial catabolism. Here, we characterize a Ni(2+)-dependent heterohexameric enzyme (MetCaCb) from the ureohydrolase superfamily, catalyzing the hydrolysis of metformin into guanylurea and dimethylamine. Either subunit alone is catalytically inactive, but together they work as an active enzyme highly specific for metformin. The crystal structure of the MetCaCb complex shows the coordination of the binuclear metal cluster only in MetCa, with MetCb as a protein binder of its active cognate. An in-silico search and functional assay discover a group of MetCaCb-like protein pairs exhibiting metformin hydrolase activity in the environment. Our findings not only establish the genetic and biochemical foundation for metformin catabolism but also provide additional insights into the adaption of the ancient enzymes toward newly occurred substrate. Discovery of a Ni(2+)-dependent heterohexameric metformin hydrolase.,Li T, Xu ZJ, Zhang ST, Xu J, Pan P, Zhou NY Nat Commun. 2024 Jul 20;15(1):6121. doi: 10.1038/s41467-024-50409-7. PMID:39033196 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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