1t8p
Crystal structure of Human erythrocyte 2,3-bisphosphoglycerate mutase
Structural highlights
DiseasePMGE_HUMAN Defects in BPGM are the cause of bisphosphoglycerate mutase deficiency (BPGMD) [MIM:222800. A disease characterized by hemolytic anemia, splenomegaly, cholelithiasis and cholecystitis.[1] [2] [3] FunctionPMGE_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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBisphosphoglycerate mutase is a trifunctional enzyme of which the main function is to synthesize 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin. The gene coding for bisphosphoglycerate mutase from the human cDNA library was cloned and expressed in Escherichia coli. The protein crystals were obtained and diffract to 2.5 A and produced the first crystal structure of bisphosphoglycerate mutase. The model was refined to a crystallographic R-factor of 0.200 and R(free) of 0.266 with excellent stereochemistry. The enzyme remains a dimer in the crystal. The overall structure of the enzyme resembles that of the cofactor-dependent phosphoglycerate mutase except the regions of 13-21, 98-117, 127-151, and the C-terminal tail. The conformational changes in the backbone and the side chains of some residues reveal the structural basis for the different activities between phosphoglycerate mutase and bisphosphoglycerate mutase. The bisphosphoglycerate mutase-specific residue Gly-14 may cause the most important conformational changes, which makes the side chain of Glu-13 orient toward the active site. The positions of Glu-13 and Phe-22 prevent 2,3-bisphosphoglycerate from binding in the way proposed previously. In addition, the side chain of Glu-13 would affect the Glu-89 protonation ability responsible for the low mutase activity. Other structural variations, which could be connected with functional differences, are also discussed. Crystal structure of human bisphosphoglycerate mutase.,Wang Y, Wei Z, Bian Q, Cheng Z, Wan M, Liu L, Gong W J Biol Chem. 2004 Sep 10;279(37):39132-8. Epub 2004 Jul 16. PMID:15258155[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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