View source for 9scy


==The R90H clinical variant of human bisphosphoglycerate mutase (hBPGM)==
<StructureSection load='9scy' size='340' side='right'caption='[[9scy]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9scy]] is a 4 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=9SCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SCY FirstGlance]. <br>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=9scy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9scy OCA], [https://pdbe.org/9scy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9scy RCSB], [https://www.ebi.ac.uk/pdbsum/9scy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9scy ProSAT]</span></td></tr>
</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 ==
Erythrocyte bisphosphoglycerate mutase (BPGM) plays a major role in regulating hemoglobin (Hb) oxygen affinity by controlling levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG). Besides its well-documented function in glycolysis, BPGM has been proposed as a regulator of serine pathway flux via 3-phosphoglycerate and as an antimalarial target. In humans, BPGM malfunction reduces intracellular concentrations of 2,3-BPG, producing a leftward shift in the hemoglobinâoxygen dissociation curve. This shift enhances the affinity of hemoglobin for oxygen, thereby impairing oxygen release to peripheral tissues. The resulting tissue hypoxia induces a compensatory erythropoietic response that clinically manifests as polycythemia/ erythrocytosis, characteristic of familial erythrocytosis type 8 (ECYT8). BPGM deficiency is rare, and a comprehensive study has been conducted in only a few patients with this disease, revealing different missense mutations. In the present study, we structurally characterized clinical variants of human BPGM (hBPGM), i.e., Arg62Gln, Arg90Cys, Arg90His, and Gln102Lys, in order to explore the molecular basis of this rare disease. Analysis of the four structural models and of a new citrate-bound hBPGM structure yielded a partial description of further open/closed conformational changes associated with enzyme activity.

New human bisphosphoglycerate mutase structures provide insights into the structural basis of BPGM deficiency and citrate inhibition.,Martinez-Rodriguez S, Torres JM, Sanchez P, Ortega E, Gavira JA Int J Biol Macromol. 2026 Jan;338(Pt 1):149491. doi: , 10.1016/j.ijbiomac.2025.149491. Epub 2025 Dec 5. PMID:41354380<ref>PMID:41354380</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9scy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gavira JA]]
[[Category: Martinez-Rodriguez S]]