7n3s

Human bisphosphoglycerate mutase complex with 2-phosphoglycolate

spinqualitylabelsall models 7n3s, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7n3s 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: PGA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease PMGE_HUMAN Defects in BPGM are the cause of bisphosphoglycerate mutase deficiency (BPGMD) [MIM:222800. A disease characterized by hemolytic anemia, splenomegaly, cholelithiasis and cholecystitis. Function PMGE_HUMAN Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.1) and phosphatase (EC 3.1.3.13) activities. Publication Abstract from PubMed Bisphosphoglycerate mutase (BPGM) is an erythrocyte-specific multifunctional enzyme that is responsible for the regulation of 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells through its synthase and phosphatase activities; the latter enzymatic function is stimulated by the endogenous activator 2-phosphoglycolate (2-PG). 2,3-BPG is a natural allosteric effector of hemoglobin (Hb) that is responsible for decreasing the affinity of Hb for oxygen to facilitate tissue oxygenation. Here, crystal structures of BPGM with 2-PG in the presence and absence of 3-phosphoglycerate are reported at 2.25 and 2.48 A resolution, respectively. Structure analysis revealed a new binding site for 2-PG at the dimer interface for the first time, in addition to the expected active-site binding. Also, conformational non-equivalence of the two active sites was observed as one of the sites was found in an open conformation, with the residues at the active-site entrance, including Arg100, Arg116 and Arg117, and the C-terminus disordered. The kinetic result is consistent with the binding of 2-PG to an allosteric or noncatalytic site as well as the active site. This study paves the way for the rational targeting of BPGM for therapeutic purposes, especially for the treatment of sickle cell disease. Molecular insight into 2-phosphoglycolate activation of the phosphatase activity of bisphosphoglycerate mutase.,Aljahdali AS, Musayev FN, Burgner JW 2nd, Ghatge MS, Shekar V, Zhang Y, Omar AM, Safo MK Acta Crystallogr D Struct Biol. 2022 Apr 1;78(Pt 4):472-482. doi:, 10.1107/S2059798322001802. Epub 2022 Mar 11. PMID:35362470 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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