5vin: Difference between revisions
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<StructureSection load='5vin' size='340' side='right' caption='[[5vin]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='5vin' size='340' side='right' caption='[[5vin]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5vin]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VIN FirstGlance]. <br> | <table><tr><td colspan='2'>[[5vin]] 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=5VIN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VIN FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5epc|5epc]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5epc|5epc]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PGM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoglucomutase Phosphoglucomutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.2.2 5.4.2.2] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoglucomutase Phosphoglucomutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.2.2 5.4.2.2] </span></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=5vin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vin OCA], [http://pdbe.org/5vin PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vin RCSB], [http://www.ebi.ac.uk/pdbsum/5vin PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vin ProSAT]</span></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=5vin FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vin OCA], [http://pdbe.org/5vin PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vin RCSB], [http://www.ebi.ac.uk/pdbsum/5vin PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vin ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PGM1_HUMAN PGM1_HUMAN]] This enzyme participates in both the breakdown and synthesis of glucose. | [[http://www.uniprot.org/uniprot/PGM1_HUMAN PGM1_HUMAN]] This enzyme participates in both the breakdown and synthesis of glucose. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human phosphoglucomutase 1 (PGM1) plays a central role in cellular glucose homeostasis, catalyzing the conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, missense variants of this enzyme were identified as causing an inborn error of metabolism, PGM1 deficiency, with features of a glycogen storage disease and a congenital disorder of glycosylation. Previous studies of selected PGM1 variants have revealed various mechanisms for enzyme dysfunction, including regions of structural disorder and side-chain rearrangements within the active site. Here, we examine variants within a substrate-binding loop in domain 4 (D4) of PGM1 that cause extreme impairment of activity. Biochemical, structural, and computational studies demonstrate multiple detrimental impacts resulting from these variants, including loss of conserved ligand-binding interactions and reduced mobility of the D4 loop, due to perturbation of its conformational ensemble. These potentially synergistic effects make this conserved ligand-binding loop a hotspot for disease-related variants in PGM1 and related enzymes. | |||
A Hotspot for Disease-Associated Variants of Human PGM1 Is Associated with Impaired Ligand Binding and Loop Dynamics.,Stiers KM, Beamer LJ Structure. 2018 Aug 7. pii: S0969-2126(18)30251-X. doi:, 10.1016/j.str.2018.07.005. PMID:30122451<ref>PMID:30122451</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5vin" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Phosphoglucomutase]] | [[Category: Phosphoglucomutase]] | ||
[[Category: Beamer, L J]] | [[Category: Beamer, L J]] | ||
Revision as of 13:21, 5 September 2018
Crystal Structure of the R515Q missense variant of human PGM1Crystal Structure of the R515Q missense variant of human PGM1
Structural highlights
Disease[PGM1_HUMAN] PGM-CDG;Glycogen storage disease due to phosphoglucomutase deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function[PGM1_HUMAN] This enzyme participates in both the breakdown and synthesis of glucose. Publication Abstract from PubMedHuman phosphoglucomutase 1 (PGM1) plays a central role in cellular glucose homeostasis, catalyzing the conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, missense variants of this enzyme were identified as causing an inborn error of metabolism, PGM1 deficiency, with features of a glycogen storage disease and a congenital disorder of glycosylation. Previous studies of selected PGM1 variants have revealed various mechanisms for enzyme dysfunction, including regions of structural disorder and side-chain rearrangements within the active site. Here, we examine variants within a substrate-binding loop in domain 4 (D4) of PGM1 that cause extreme impairment of activity. Biochemical, structural, and computational studies demonstrate multiple detrimental impacts resulting from these variants, including loss of conserved ligand-binding interactions and reduced mobility of the D4 loop, due to perturbation of its conformational ensemble. These potentially synergistic effects make this conserved ligand-binding loop a hotspot for disease-related variants in PGM1 and related enzymes. A Hotspot for Disease-Associated Variants of Human PGM1 Is Associated with Impaired Ligand Binding and Loop Dynamics.,Stiers KM, Beamer LJ Structure. 2018 Aug 7. pii: S0969-2126(18)30251-X. doi:, 10.1016/j.str.2018.07.005. PMID:30122451[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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