7bsj

Crystal structure of human ME2 R484W

spinqualitylabelsall models 7bsj, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bsj is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.48Å Ligands: FUM, MG, NAD, TTN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MAOM_HUMAN Publication Abstract from PubMed Human mitochondrial NAD(P)(+)-dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. Two ME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating "dead form," and ME2_R484W was an overactivating "closed form" of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes. Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P)(+)-dependent malic enzyme.,Hsieh JY, Yang HP, Tewary SK, Cheng HC, Liu YL, Tai SC, Chen WL, Hsu CH, Huang TJ, Chou CJ, Huang YN, Peng CT, Ho MC, Liu GY, Hung HC iScience. 2021 Jan 13;24(2):102034. doi: 10.1016/j.isci.2021.102034. eCollection , 2021 Feb 19. PMID:33554057 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Malate Dehydrogenase 3D structures

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