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7tl7

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Current revision

1.90A resolution structure of independent phosphoglycerate mutase from C. elegans in complex with a macrocyclic peptide inhibitor (Sa-D2)

Structural highlights

7tl7 is a 8 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 1.9Å
Ligands:	, , , , , ,
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

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^[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: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
↑ van Neer RHP, Dranchak PK, Liu L, Aitha M, Queme B, Kimura H, Katoh T, Battaile KP, Lovell S, Inglese J, Suga H. Serum-Stable and Selective Backbone-N-Methylated Cyclic Peptides That Inhibit Prokaryotic Glycolytic Mutases. ACS Chem Biol. 2022 Aug 19;17(8):2284-2295. doi: 10.1021/acschembio.2c00403. Epub, 2022 Jul 29. PMID:35904259 doi:http://dx.doi.org/10.1021/acschembio.2c00403

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7tl7"

@@ Line 4: / Line 4: @@
 == 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='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>
+</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>
+[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 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7tl7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoglycerate mutase 3D structures|Phosphoglycerate mutase 3D structures]]
 == References ==
 <references/>

7tl7

From Proteopedia

Current revision

1.90A resolution structure of independent phosphoglycerate mutase from C. elegans in complex with a macrocyclic peptide inhibitor (Sa-D2)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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