6ojd: Difference between revisions
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==A high-resolution crystal structure of covalent complex of NocB thioesterase domain with fluorophosphonate nocardicin G analog== | |||
<StructureSection load='6ojd' size='340' side='right'caption='[[6ojd]], [[Resolution|resolution]] 1.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ojd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Nocardia_uniformis_subsp._tsuyamanensis Nocardia uniformis subsp. tsuyamanensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OJD 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]] 1.99Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MUY:(R)-[(S)-[(3S)-3-{[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino}-2-oxoazetidin-1-yl](4-hydroxyphenyl)methyl]methylphosphinic+acid'>MUY</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=6ojd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ojd OCA], [https://pdbe.org/6ojd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ojd RCSB], [https://www.ebi.ac.uk/pdbsum/6ojd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ojd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q5J1Q6_NOCUT Q5J1Q6_NOCUT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Nonribosomal peptide synthetases (NRPSs) underlie the biosynthesis of many natural products that have important medicinal utility. Protection of the NRPS peptide products from proteolysis is critical to these pathways and is often achieved by structural modification, principally the introduction of D-amino acid residues into the elongating peptide. These amino acids are generally formed in situ from their L-stereoisomers by epimerization domains or dual-function condensation/epimerization domains. In singular contrast, the thioesterase domain of nocardicin biosynthesis mediates both the effectively complete L- to D-epimerization of its C-terminal amino acid residue (>/=100:1) and hydrolytic product release. We report herein high-resolution crystal structures of the nocardicin thioesterase domain in ligand-free form and reacted with a structurally precise fluorophosphonate substrate mimic that identify the complete peptide binding pocket to accommodate both stereoisomers. These structures combined with additional functional studies provide detailed mechanistic insight into this unique dual-function NRPS domain. | |||
Structure of a bound peptide phosphonate reveals the mechanism of nocardicin bifunctional thioesterase epimerase-hydrolase half-reactions.,Patel KD, d'Andrea FB, Gaudelli NM, Buller AR, Townsend CA, Gulick AM Nat Commun. 2019 Aug 27;10(1):3868. doi: 10.1038/s41467-019-11740-6. PMID:31455765<ref>PMID:31455765</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6ojd" style="background-color:#fffaf0;"></div> | ||
[[Category: Gulick | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Nocardia uniformis subsp. tsuyamanensis]] | |||
[[Category: Gulick AM]] | |||
[[Category: Patel KD]] | |||
Latest revision as of 10:11, 11 October 2023
A high-resolution crystal structure of covalent complex of NocB thioesterase domain with fluorophosphonate nocardicin G analogA high-resolution crystal structure of covalent complex of NocB thioesterase domain with fluorophosphonate nocardicin G analog
Structural highlights
FunctionPublication Abstract from PubMedNonribosomal peptide synthetases (NRPSs) underlie the biosynthesis of many natural products that have important medicinal utility. Protection of the NRPS peptide products from proteolysis is critical to these pathways and is often achieved by structural modification, principally the introduction of D-amino acid residues into the elongating peptide. These amino acids are generally formed in situ from their L-stereoisomers by epimerization domains or dual-function condensation/epimerization domains. In singular contrast, the thioesterase domain of nocardicin biosynthesis mediates both the effectively complete L- to D-epimerization of its C-terminal amino acid residue (>/=100:1) and hydrolytic product release. We report herein high-resolution crystal structures of the nocardicin thioesterase domain in ligand-free form and reacted with a structurally precise fluorophosphonate substrate mimic that identify the complete peptide binding pocket to accommodate both stereoisomers. These structures combined with additional functional studies provide detailed mechanistic insight into this unique dual-function NRPS domain. Structure of a bound peptide phosphonate reveals the mechanism of nocardicin bifunctional thioesterase epimerase-hydrolase half-reactions.,Patel KD, d'Andrea FB, Gaudelli NM, Buller AR, Townsend CA, Gulick AM Nat Commun. 2019 Aug 27;10(1):3868. doi: 10.1038/s41467-019-11740-6. PMID:31455765[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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