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| | ==The Structure of Human Bisphosphoglycerate Mutase to 1.94A== | | ==The Structure of Human Bisphosphoglycerate Mutase to 1.94A== |
| - | <StructureSection load='3nfy' size='340' side='right' caption='[[3nfy]], [[Resolution|resolution]] 1.94Å' scene=''> | + | <StructureSection load='3nfy' size='340' side='right'caption='[[3nfy]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nfy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NFY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NFY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nfy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NFY FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BPGM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BPGM ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfy OCA], [http://pdbe.org/3nfy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nfy RCSB], [http://www.ebi.ac.uk/pdbsum/3nfy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nfy ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfy OCA], [https://pdbe.org/3nfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nfy RCSB], [https://www.ebi.ac.uk/pdbsum/3nfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nfy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PMGE_HUMAN PMGE_HUMAN]] Defects in BPGM are the cause of bisphosphoglycerate mutase deficiency (BPGMD) [MIM:[http://omim.org/entry/222800 222800]]. A disease characterized by hemolytic anemia, splenomegaly, cholelithiasis and cholecystitis.<ref>PMID:2542247</ref> <ref>PMID:1421379</ref> <ref>PMID:15054810</ref> | + | [[https://www.uniprot.org/uniprot/PMGE_HUMAN PMGE_HUMAN]] Defects in BPGM are the cause of bisphosphoglycerate mutase deficiency (BPGMD) [MIM:[https://omim.org/entry/222800 222800]]. A disease characterized by hemolytic anemia, splenomegaly, cholelithiasis and cholecystitis.<ref>PMID:2542247</ref> <ref>PMID:1421379</ref> <ref>PMID:15054810</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PMGE_HUMAN 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. | + | [[https://www.uniprot.org/uniprot/PMGE_HUMAN 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Phosphoglycerate Mutase|Phosphoglycerate Mutase]] | + | *[[Phosphoglycerate mutase 3D structures|Phosphoglycerate mutase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Nairn, J]] | | [[Category: Nairn, J]] |
| | [[Category: Patterson, A F]] | | [[Category: Patterson, A F]] |
| Structural highlights
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.[1] [2] [3]
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
Erythrocyte-specific bisphosphoglycerate mutase is a trifunctional enzyme which modulates the levels of 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells by virtue of its synthase and phosphatase activities. Low levels of erythrocyte 2,3-BPG increase the affinity of haemoglobin for oxygen, thus limiting the release of oxygen into tissues. 2,3-BPG levels in stored blood decline rapidly owing to the phosphatase activity of bisphosphoglycerate mutase, which is enhanced by a fall in pH. Here, the 1.94 A resolution X-ray structure of bisphosphoglycerate mutase is presented, focusing on the dynamic nature of key ligand-binding residues and their interaction with the inhibitor citrate. Residues at the binding pocket are complete. In addition, the movement of key residues in the presence and absence of ligand is described and alternative conformations are explored. The conformation in which the ligand citrate would bind at the substrate-binding pocket is proposed, with discussion and representations of its orientation. The characterization of bisphosphoglycerate mutase-citrate interactions will provide a framework for the design of specific inhibitors of the phosphatase activity of this enzyme, which may limit the decline of 2,3-BPG in stored blood.
Unliganded structure of human bisphosphoglycerate mutase reveals side-chain movements induced by ligand binding.,Patterson A, Price NC, Nairn J Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Nov 1;66(Pt, 11):1415-20. Epub 2010 Oct 27. PMID:21045285[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rosa R, Blouquit Y, Calvin MC, Prome D, Prome JC, Rosa J. Isolation, characterization, and structure of a mutant 89 Arg----Cys bisphosphoglycerate mutase. Implication of the active site in the mutation. J Biol Chem. 1989 May 15;264(14):7837-43. PMID:2542247
- ↑ Lemarchandel V, Joulin V, Valentin C, Rosa R, Galacteros F, Rosa J, Cohen-Solal M. Compound heterozygosity in a complete erythrocyte bisphosphoglycerate mutase deficiency. Blood. 1992 Nov 15;80(10):2643-9. PMID:1421379
- ↑ Hoyer JD, Allen SL, Beutler E, Kubik K, West C, Fairbanks VF. Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Am J Hematol. 2004 Apr;75(4):205-8. PMID:15054810 doi:10.1002/ajh.20014
- ↑ Patterson A, Price NC, Nairn J. Unliganded structure of human bisphosphoglycerate mutase reveals side-chain movements induced by ligand binding. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Nov 1;66(Pt, 11):1415-20. Epub 2010 Oct 27. PMID:21045285 doi:10.1107/S1744309110035475
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