5d2r: Difference between revisions
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==Inhibitor Bound Cell Shape Determinant Protein Csd4 from Helicobacter pylori== | ==Inhibitor Bound Cell Shape Determinant Protein Csd4 from Helicobacter pylori== | ||
<StructureSection load='5d2r' size='340' side='right' caption='[[5d2r]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='5d2r' size='340' side='right'caption='[[5d2r]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5d2r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D2R OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5d2r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori_G27 Helicobacter pylori G27]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D2R FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=56W:(2R,6R)-2-{[(R)-[(3R)-3-(ACETYLAMINO)-3-CARBOXYPROPYL](HYDROXY)PHOSPHORYL]METHYL}-6-AMINOHEPTANEDIOIC+ACID'>56W</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 1.9Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=56W:(2R,6R)-2-{[(R)-[(3R)-3-(ACETYLAMINO)-3-CARBOXYPROPYL](HYDROXY)PHOSPHORYL]METHYL}-6-AMINOHEPTANEDIOIC+ACID'>56W</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=5d2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d2r OCA], [https://pdbe.org/5d2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d2r RCSB], [https://www.ebi.ac.uk/pdbsum/5d2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d2r ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/B5ZAD9_HELPG B5ZAD9_HELPG] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Helicobacter pylori G27]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Chan AC]] | ||
[[Category: | [[Category: Murphy ME]] | ||
Latest revision as of 11:42, 27 September 2023
Inhibitor Bound Cell Shape Determinant Protein Csd4 from Helicobacter pyloriInhibitor Bound Cell Shape Determinant Protein Csd4 from Helicobacter pylori
Structural highlights
FunctionPublication Abstract from PubMedHelicobacter pylori and Campylobacter jejuni are human pathogens and causative agents of gastric ulcers/cancer and gastroenteritis, respectively. Recent studies have uncovered a series of proteases that are responsible for maintaining the helical shape of these organisms. The H. pylori metalloprotease Csd4 and its C. jejuni homologue Pgp1 cleave the amide bond between meso-diaminopimelate and iso-d-glutamic acid in truncated peptidoglycan side chains. Deletion of either csd4 or pgp1 results in bacteria with a straight rod phenotype, a reduced ability to move in viscous media, and reduced pathogenicity. In this work, a phosphinic acid-based pseudodipeptide inhibitor was designed to act as a tetrahedral intermediate analog against the Csd4 enzyme. The phosphinic acid was shown to inhibit the cleavage of the alternate substrate, Ac-l-Ala-iso-d-Glu-meso-Dap, with a Ki value of 1.5 muM. Structural analysis of the Csd4-inhibitor complex shows that the phosphinic acid displaces the zinc-bound water and chelates the metal in a bidentate fashion. The phosphinate oxygens also interact with the key acid/base residue, Glu222, and the oxyanion-stabilizing residue, Arg86. The results are consistent with the "promoted-water pathway" mechanism for carboxypeptidase A catalysis. Studies on cultured bacteria showed that the inhibitor causes significant cell straightening when incubated with H. pylori at millimolar concentrations. A diminished, yet observable, effect on the morphology of C. jejuni was also apparent. Cell straightening was more pronounced with an acapsular C. jejuni mutant strain compared to the wild type, suggesting that the capsule impaired inhibitor accessibility. These studies demonstrate that a highly polar compound is capable of crossing the outer membrane and altering cell shape, presumably by inhibiting cell shape determinant proteases. Peptidoglycan proteases acting as cell shape determinants represent novel targets for the development of antimicrobials against these human pathogens. A Bacterial Cell Shape-Determining Inhibitor.,Liu Y, Frirdich E, Taylor JA, Chan AC, Blair KM, Vermeulen J, Ha R, Murphy ME, Salama NR, Gaynor EC, Tanner ME ACS Chem Biol. 2016 Jan 15. PMID:26735022[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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