6lpp

Crystal structure of human D-2-hydroxyglutarate dehydrogenase in complex with D-2-hydroxyglutarate (D-2-HG)

spinqualitylabelsall models 6lpp, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6lpp 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 2.65Å Ligands: 2HG, FAD, GOL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease D2HDH_HUMAN D-2-hydroxyglutaric aciduria. The disease is caused by variants affecting the gene represented in this entry. Function D2HDH_HUMAN Catalyzes the oxidation of D-2-hydroxyglutarate to alpha-ketoglutarate. Publication Abstract from PubMed D-2-hydroxyglutarate dehydrogenase (D-2-HGDH) catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) into 2-oxoglutarate, and genetic D-2-HGDH deficiency leads to abnormal accumulation of D-2-HG which causes type I D-2-hydroxyglutaric aciduria and is associated with diffuse large B-cell lymphoma. This work reports the crystal structures of human D-2-HGDH in apo form and in complexes with D-2-HG, D-malate, D-lactate, L-2-HG, and 2-oxoglutarate, respectively. D-2-HGDH comprises a FAD-binding domain, a substrate-binding domain, and a small C-terminal domain. The active site is located at the interface of the FAD-binding domain and the substrate-binding domain. The functional roles of the key residues involved in the substrate binding and catalytic reaction and the mutations identified in D-2-HGDH-deficient diseases are analyzed by biochemical studies. The structural and biochemical data together reveal the molecular mechanism of the substrate specificity and catalytic reaction of D-2-HGDH and provide insights into the pathogenicity of the disease-associated mutations. Structure, substrate specificity, and catalytic mechanism of human D-2-HGDH and insights into pathogenicity of disease-associated mutations.,Yang J, Zhu H, Zhang T, Ding J Cell Discov. 2021 Jan 12;7(1):3. doi: 10.1038/s41421-020-00227-0. PMID:33431826 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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