View source for 6cfs


==Structure of Human alpha-Phosphomannomutase 1 containing mutation M186Q==
<StructureSection load='6cfs' size='340' side='right'caption='[[6cfs]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cfs]] is a 1 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=6CFS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CFS 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]] 2.07&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6cfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cfs OCA], [https://pdbe.org/6cfs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cfs RCSB], [https://www.ebi.ac.uk/pdbsum/6cfs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cfs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PMM1_HUMAN PMM1_HUMAN] Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. In addition, may be responsible for the degradation of glucose-1,6-bisphosphate in ischemic brain.
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== Publication Abstract from PubMed ==
The human phosphomannomutases PMM1 and PMM2 catalyze the interconversion of hexose 6-phosphates and hexose 1-phosphates. The two isoforms share 66% sequence identity and have similar kinetic properties as mutases in vitro, but differ in their functional roles in vivo. Though the physiological role of PMM2 is catalysis of the mutase reaction that provides the mannose 1-phosphate (Man-1-P) essential for protein glycosylation, PMM1 is thought to provide a phosphohydrolase activity in the presence of inosine monophosphate (IMP), converting glucose 1,6-bisphosphate (Glu-1,6-P2) to glucose 6-phosphate (Glu-6-P), rescuing glycolysis during brain ischemia. To uncover the structural basis of how IMP binding converts PMM1 from a mutase to a phosphatase, the 1.93 A resolution structure of PMM1 complexed with IMP was determined. The structure reveals IMP bound at the substrate recruitment site, thus inhibiting the mutase activity while simultaneous activating a phosphatase activity (IMP Kact = 1.5 muM) resulting from the hydrolysis of the phospho-enzyme. The bound structure and site-directed mutagenesis confirm that the long-range electrostatic interactions provided by Arg180 and Arg183 conserved in PMM1 are the major contributors to IMP binding, and their oblation removes phosphatase but not mutase activity. These residues are not present in the PMM2 isoform, which consequently lacks significant phosphatase activity in the presence of IMP. T2 relaxation NMR and SAXS together support the hypothesis that IMP binding to PMM1 favors an enzyme conformation that is catalytically competent for water attack at the phosphoaspartyl intermediate. Such a mechanism may be generalizable to other enzymes that act through covalent intermediates.

The structural basis of the molecular switch between phosphatase and mutase functions of human phosphomannomutase 1 under ischemic conditions.,Ji T, Zhang C, Zheng L, Dunaway-Mariano D, Allen KN Biochemistry. 2018 Apr 25. doi: 10.1021/acs.biochem.8b00223. PMID:29695157<ref>PMID:29695157</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6cfs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphomannomutase|Phosphomannomutase]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Allen KN]]
[[Category: Dunaway-Mariano D]]
[[Category: Ji T]]