5kgn | pdb_00005kgn

1.95A resolution structure of independent phosphoglycerate mutase from C. elegans in complex with a macrocyclic peptide inhibitor (2d)

spinqualitylabelsall models 5kgn, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5kgn is a 4 chain structure with sequence from Caenorhabditis elegans and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: ACE, CL, DTY, GOL, MG, MN, NH2, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GPMI_CAEEL Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoglycerate mutase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA