7n3s: Difference between revisions
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==Human bisphosphoglycerate mutase complex with 2-phosphoglycolate== | ==Human bisphosphoglycerate mutase complex with 2-phosphoglycolate== | ||
<StructureSection load='7n3s' size='340' side='right'caption='[[7n3s]]' scene=''> | <StructureSection load='7n3s' size='340' side='right'caption='[[7n3s]], [[Resolution|resolution]] 2.48Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N3S FirstGlance]. <br> | <table><tr><td colspan='2'>[[7n3s]] 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=7N3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N3S FirstGlance]. <br> | ||
</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=7n3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n3s OCA], [https://pdbe.org/7n3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n3s RCSB], [https://www.ebi.ac.uk/pdbsum/7n3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n3s ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.48Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PGA:2-PHOSPHOGLYCOLIC+ACID'>PGA</scene></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=7n3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n3s OCA], [https://pdbe.org/7n3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n3s RCSB], [https://www.ebi.ac.uk/pdbsum/7n3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n3s ProSAT]</span></td></tr> | |||
</table> | </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. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:35362470</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7n3s" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Aljahdali AS]] | [[Category: Aljahdali AS]] | ||
[[Category: Musayev FN]] | [[Category: Musayev FN]] | ||
[[Category: Safo MK]] | [[Category: Safo MK]] | ||
Latest revision as of 19:23, 18 October 2023
Human bisphosphoglycerate mutase complex with 2-phosphoglycolateHuman bisphosphoglycerate mutase complex with 2-phosphoglycolate
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. Publication Abstract from PubMedBisphosphoglycerate 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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