7tl7: Difference between revisions

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-'''Unreleased structure'''
-The entry 7tl7 is ON HOLD  until Paper Publication
+==1.90A resolution structure of independent phosphoglycerate mutase from C. elegans in complex with a macrocyclic peptide inhibitor (Sa-D2)==
+<StructureSection load='7tl7' size='340' side='right'caption='[[7tl7]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7tl7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TL7 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]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=YNM:N-METHYL-L-TYROSINE'>YNM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7tl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tl7 OCA], [https://pdbe.org/7tl7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tl7 RCSB], [https://www.ebi.ac.uk/pdbsum/7tl7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tl7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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 ==
+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.
-Authors: Liu, L., Lovell, S., Battaile, K.P., Dranchak, P., Queme, B., Aitha, M., van Neer, R.H.P., Kimura, H., Katho, T., Suga, H., Inglese, J.
+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<ref>PMID:35904259</ref>
-Description: 1.90A resolution structure of independent phosphoglycerate mutase from C. elegans in complex with a macrocyclic peptide inhibitor (Sa-D2)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Inglese, J]]
+<div class="pdbe-citations 7tl7" style="background-color:#fffaf0;"></div>
-[[Category: Suga, H]]
-[[Category: Van Neer, R.H.P]]
+==See Also==
-[[Category: Battaile, K.P]]
+*[[Phosphoglycerate mutase 3D structures|Phosphoglycerate mutase 3D structures]]
-[[Category: Dranchak, P]]
+== References ==
-[[Category: Liu, L]]
+<references/>
-[[Category: Katho, T]]
+__TOC__
-[[Category: Lovell, S]]
+</StructureSection>
-[[Category: Aitha, M]]
+[[Category: Caenorhabditis elegans]]
-[[Category: Kimura, H]]
+[[Category: Large Structures]]
-[[Category: Queme, B]]
+[[Category: Synthetic construct]]
+[[Category: Aitha M]]
+[[Category: Battaile KP]]
+[[Category: Dranchak P]]
+[[Category: Inglese J]]
+[[Category: Katho T]]
+[[Category: Kimura H]]
+[[Category: Liu L]]
+[[Category: Lovell S]]
+[[Category: Queme B]]
+[[Category: Suga H]]
+[[Category: Van Neer RHP]]