5kgl: Difference between revisions

Latest revision as of 10:00, 27 September 2023

2.45A resolution structure of Apo independent phosphoglycerate mutase from C. elegans (orthorhombic form)

Structural highlights

5kgl is a 2 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.45Å
Ligands:	CL, MN, SO4, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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:https://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:https://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:https://dx.doi.org/10.1038/ncomms14932

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OCA

[1] 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:https://dx.doi.org/10.1074/jbc.M405877200

[2] 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:https://dx.doi.org/10.1016/j.molbiopara.2007.08.002

[3] 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:https://dx.doi.org/10.1038/ncomms14932

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='5kgl' size='340' side='right'caption='[[5kgl]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5kgl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KGL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KGL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5kgl]] 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=5KGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KGL FirstGlance]. <br>
-</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=SO4:SULFATE+ION'>SO4</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]] 2.45&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kgn|5kgn]], [[5kgm|5kgm]]</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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5kgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kgl OCA], [https://pdbe.org/5kgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kgl RCSB], [https://www.ebi.ac.uk/pdbsum/5kgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kgl ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5kgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kgl OCA], [http://pdbe.org/5kgl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kgl RCSB], [http://www.ebi.ac.uk/pdbsum/5kgl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kgl ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Caenorhabditis elegans]]
 [[Category: Large Structures]]
-[[Category: Battaile, K P]]
+[[Category: Battaile KP]]
-[[Category: Carlow, T]]
+[[Category: Carlow T]]
-[[Category: Dranchak, P]]
+[[Category: Dranchak P]]
-[[Category: Inglese, J]]
+[[Category: Inglese J]]
-[[Category: Li, Z]]
+[[Category: Li Z]]
-[[Category: Lovell, S]]
+[[Category: Lovell S]]
-[[Category: MacArthur, R]]
+[[Category: MacArthur R]]
-[[Category: Mehzabeen, N]]
+[[Category: Mehzabeen N]]
-[[Category: Suga, H]]
+[[Category: Suga H]]
-[[Category: Yu, H]]
+[[Category: Yu H]]
-[[Category: Coupled enzyme assay]]
-[[Category: High throughput enzymology]]
-[[Category: Ht]]
-[[Category: Isomerase]]
-[[Category: Metal binding]]
-[[Category: Rapid system]]
-[[Category: Structure activity relationship]]

5kgl: Difference between revisions

Latest revision as of 10:00, 27 September 2023

2.45A resolution structure of Apo independent phosphoglycerate mutase from C. elegans (orthorhombic form)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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