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| | ==2.95A resolution structure of Apo independent phosphoglycerate mutase from C. elegans (monoclinic form)== | | ==2.95A resolution structure of Apo independent phosphoglycerate mutase from C. elegans (monoclinic form)== |
| - | <StructureSection load='5kgm' size='340' side='right' caption='[[5kgm]], [[Resolution|resolution]] 2.95Å' scene=''> | + | <StructureSection load='5kgm' size='340' side='right'caption='[[5kgm]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kgm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KGM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KGM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kgm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KGM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KGM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 2.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kgn|5kgn]], [[5kgl|5kgl]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ipgm-1, F57B10.3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</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=5kgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kgm OCA], [https://pdbe.org/5kgm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kgm RCSB], [https://www.ebi.ac.uk/pdbsum/5kgm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kgm ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoglycerate_mutase_(2,3-diphosphoglycerate-independent) Phosphoglycerate mutase (2,3-diphosphoglycerate-independent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.2.12 5.4.2.12] </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=5kgm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kgm OCA], [http://pdbe.org/5kgm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kgm RCSB], [http://www.ebi.ac.uk/pdbsum/5kgm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kgm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GPMI_CAEEL GPMI_CAEEL]] Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate.<ref>PMID:15234973</ref> <ref>PMID:17897734</ref> | + | [https://www.uniprot.org/uniprot/GPMI_CAEEL GPMI_CAEEL] Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate.<ref>PMID:15234973</ref> <ref>PMID:17897734</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5kgm" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5kgm" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phosphoglycerate mutase 3D structures|Phosphoglycerate mutase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| - | [[Category: Battaile, K P]] | + | [[Category: Large Structures]] |
| - | [[Category: Carlow, T]] | + | [[Category: Battaile KP]] |
| - | [[Category: Dranchak, P]] | + | [[Category: Carlow T]] |
| - | [[Category: Inglese, J]] | + | [[Category: Dranchak P]] |
| - | [[Category: Li, Z]] | + | [[Category: Inglese J]] |
| - | [[Category: Lovell, S]] | + | [[Category: Li Z]] |
| - | [[Category: MacArthur, R]] | + | [[Category: Lovell S]] |
| - | [[Category: Mehzabeen, N]] | + | [[Category: MacArthur R]] |
| - | [[Category: Suga, H]] | + | [[Category: Mehzabeen N]] |
| - | [[Category: Yu, H]] | + | [[Category: Suga H]] |
| - | [[Category: Coupled enzyme assay]]
| + | [[Category: Yu H]] |
| - | [[Category: High throughput enzymology]]
| + | |
| - | [[Category: Ht]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Metal binding]]
| + | |
| - | [[Category: Rapid system]]
| + | |
| - | [[Category: Structure activity relationship]]
| + | |
| Structural highlights
Function
GPMI_CAEEL Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate.[1] [2]
Publication Abstract from PubMed
Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanism placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.
Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases.,Yu H, Dranchak P, Li Z, MacArthur R, Munson MS, Mehzabeen N, Baird NJ, Battalie KP, Ross D, Lovell S, Carlow CK, Suga H, Inglese J Nat Commun. 2017 Apr 3;8:14932. doi: 10.1038/ncomms14932. PMID:28368002[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Y, Foster JM, Kumar S, Fougere M, Carlow CK. Cofactor-independent phosphoglycerate mutase has an essential role in Caenorhabditis elegans and is conserved in parasitic nematodes. J Biol Chem. 2004 Aug 27;279(35):37185-90. Epub 2004 Jul 2. PMID:15234973 doi:http://dx.doi.org/10.1074/jbc.M405877200
- ↑ Raverdy S, Zhang Y, Foster J, Carlow CK. Molecular and biochemical characterization of nematode cofactor independent phosphoglycerate mutases. Mol Biochem Parasitol. 2007 Dec;156(2):210-6. Epub 2007 Aug 19. PMID:17897734 doi:http://dx.doi.org/10.1016/j.molbiopara.2007.08.002
- ↑ Yu H, Dranchak P, Li Z, MacArthur R, Munson MS, Mehzabeen N, Baird NJ, Battalie KP, Ross D, Lovell S, Carlow CK, Suga H, Inglese J. Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases. Nat Commun. 2017 Apr 3;8:14932. doi: 10.1038/ncomms14932. PMID:28368002 doi:http://dx.doi.org/10.1038/ncomms14932
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