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| - | [[Image:1t8p.gif|left|200px]] | |
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| - | <!-- | + | ==Crystal structure of Human erythrocyte 2,3-bisphosphoglycerate mutase== |
| - | The line below this paragraph, containing "STRUCTURE_1t8p", creates the "Structure Box" on the page.
| + | <StructureSection load='1t8p' size='340' side='right'caption='[[1t8p]], [[Resolution|resolution]] 2.50Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1t8p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T8P FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</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=1t8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t8p OCA], [https://pdbe.org/1t8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t8p RCSB], [https://www.ebi.ac.uk/pdbsum/1t8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t8p ProSAT]</span></td></tr> |
| - | {{STRUCTURE_1t8p| PDB=1t8p | SCENE= }}
| + | </table> |
| | + | == Disease == |
| | + | [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 == |
| | + | [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. |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t8/1t8p_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1t8p ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Bisphosphoglycerate 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 erythrocyte 2,3-bisphosphoglycerate mutase'''
| + | 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<ref>PMID:15258155</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | Bisphosphoglycerate 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.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1T8P is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T8P OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1t8p" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15258155 15258155]
| + | *[[Phosphoglycerate mutase 3D structures|Phosphoglycerate mutase 3D structures]] |
| - | [[Category: Bisphosphoglycerate mutase]] | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Bian, Q.]] | + | [[Category: Bian Q]] |
| - | [[Category: Cheng, Z.]] | + | [[Category: Cheng Z]] |
| - | [[Category: Gong, W.]] | + | [[Category: Gong W]] |
| - | [[Category: Liu, L.]] | + | [[Category: Liu L]] |
| - | [[Category: Wan, M.]] | + | [[Category: Wan M]] |
| - | [[Category: Wang, Y.]] | + | [[Category: Wang Y]] |
| - | [[Category: Wei, Z.]] | + | [[Category: Wei Z]] |
| - | [[Category: Isomerase]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:40:32 2008''
| + | |
| 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.
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 PubMed
Bisphosphoglycerate 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 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
- ↑ Wang Y, Wei Z, Bian Q, Cheng Z, Wan M, Liu L, Gong W. Crystal structure of human bisphosphoglycerate mutase. J Biol Chem. 2004 Sep 10;279(37):39132-8. Epub 2004 Jul 16. PMID:15258155 doi:10.1074/jbc.M405982200
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