5f1v: Difference between revisions
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<StructureSection load='5f1v' size='340' side='right'caption='[[5f1v]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='5f1v' size='340' side='right'caption='[[5f1v]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5f1v]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5f1v]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Campylobacter_jejuni Campylobacter jejuni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F1V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F1V FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3VN:(2R,5R)-2,5-DIAMINO-2,5-BIS(4-AMINOBUTYL)HEXANEDIOIC+ACID'>3VN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3VN:(2R,5R)-2,5-DIAMINO-2,5-BIS(4-AMINOBUTYL)HEXANEDIOIC+ACID'>3VN</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KPI:(2S)-2-AMINO-6-[(1-HYDROXY-1-OXO-PROPAN-2-YLIDENE)AMINO]HEXANOIC+ACID'>KPI</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=5f1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1v OCA], [https://pdbe.org/5f1v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f1v RCSB], [https://www.ebi.ac.uk/pdbsum/5f1v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1v ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DAPA_CAMJE DAPA_CAMJE] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).[HAMAP-Rule:MF_00418] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5f1v" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5f1v" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Dihydrodipicolinate synthase|Dihydrodipicolinate synthase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Campylobacter | [[Category: Campylobacter jejuni]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Conly | [[Category: Conly CJT]] | ||
[[Category: Palmer | [[Category: Palmer DRJ]] | ||
[[Category: Sanders | [[Category: Sanders DAR]] | ||
Latest revision as of 11:41, 12 July 2023
biomimetic design results in a potent allosteric inhibitor of dihydrodipicolinate synthase from Campylobacter jejunibiomimetic design results in a potent allosteric inhibitor of dihydrodipicolinate synthase from Campylobacter jejuni
Structural highlights
FunctionDAPA_CAMJE Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).[HAMAP-Rule:MF_00418] Publication Abstract from PubMedDihydrodipicolinate synthase (DHDPS), an enzyme required for bacterial peptidoglycan biosynthesis, catalyzes the condensation of pyruvate and beta-aspartate semialdehyde (ASA) to form a cyclic product which dehydrates to form dihydrodipicolinate. DHDPS has, for several years, been considered a putative target for novel antibiotics. We have designed the first potent inhibitor of this enzyme by mimicking its natural allosteric regulation by lysine, and obtained a crystal structure of the protein-inhibitor complex at 2.2 A resolution. This novel inhibitor, which we named "bislysine", resembles two lysine molecules linked by an ethylene bridge between the alpha-carbon atoms. Bislysine is a mixed partial inhibitor with respect to the first substrate, pyruvate, and a noncompetitive partial inhibitor with respect to ASA, and binds to all forms of the enzyme with a Ki near 200 nM, more than 300 times more tightly than lysine. Hill plots show that the inhibition is cooperative, indicating that the allosteric sites are not independent despite being located on opposite sides of the protein tetramer, separated by approximately 50 A. A mutant enzyme resistant to lysine inhibition, Y110F, is strongly inhibited by this novel inhibitor, suggesting this may be a promising strategy for antibiotic development. Biomimetic Design Results in a Potent Allosteric Inhibitor of Dihydrodipicolinate Synthase from Campylobacter jejuni.,Skovpen YV, Conly CJ, Sanders DA, Palmer DR J Am Chem Soc. 2016 Feb 17;138(6):2014-20. doi: 10.1021/jacs.5b12695. Epub 2016, Feb 2. PMID:26836694[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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