7tl8 | pdb_00007tl8

1.95A resolution structure of independent phosphoglycerate mutase from S. aureus in complex with a macrocyclic peptide inhibitor (Sa-D3)

spinqualitylabelsall models 7tl8, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7tl8 is a 2 chain structure with sequence from Staphylococcus aureus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5JP, ACE, DTY, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [W8U5L7_STAAU] Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate.[HAMAP-Rule:MF_01038] Publication Abstract from PubMed N-Methylated amino acids (N-MeAAs) are privileged residues of naturally occurring peptides critical to bioactivity. However, de novo discovery from ribosome display is limited by poor incorporation of N-methylated amino acids into the nascent peptide chain attributed to a poor EF-Tu affinity for the N-methyl-aminoacyl-tRNA. By reconfiguring the tRNA's T-stem region to compensate and tune the EF-Tu affinity, we conducted Random nonstandard Peptides Integrated Discovery (RaPID) display of a macrocyclic peptide (MCP) library containing six different N-MeAAs. We have here devised a "pool-and-split" enrichment strategy using the RaPID display and identified N-methylated MCPs against three species of prokaryotic metal-ion-dependent phosphoglycerate mutases. The enriched MCPs reached 57% N-methylation with up to three consecutively incorporated N-MeAAs, rivaling natural products. Potent nanomolar inhibitors ranging in ortholog selectivity, strongly mediated by N-methylation, were identified. Co-crystal structures reveal an architecturally related Ce-2 Ipglycermide active-site metal-ion-coordinating Cys lariat MCP, functionally dependent on two cis N-MeAAs with broadened iPGM species selectivity over the original nematode-selective MCPs. Furthermore, the isolation of a novel metal-ion-independent Staphylococcus aureus iPGM inhibitor utilizing a phosphoglycerate mimetic mechanism illustrates the diversity of possible chemotypes encoded by the N-MeAA MCP library. Serum-Stable and Selective Backbone-N-Methylated Cyclic Peptides That Inhibit Prokaryotic Glycolytic Mutases.,van Neer RHP, Dranchak PK, Liu L, Aitha M, Queme B, Kimura H, Katoh T, Battaile KP, Lovell S, Inglese J, Suga H ACS Chem Biol. 2022 Aug 19;17(8):2284-2295. doi: 10.1021/acschembio.2c00403. Epub, 2022 Jul 29. PMID:35904259 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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