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| | ==Solution structure of a Beta-Hairpin Peptidomimetic antibiotic that targets LptD in Pseudomonas sp.== | | ==Solution structure of a Beta-Hairpin Peptidomimetic antibiotic that targets LptD in Pseudomonas sp.== |
| - | <StructureSection load='2m7i' size='340' side='right' caption='[[2m7i]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2m7i' size='340' side='right'caption='[[2m7i]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m7i]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M7I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m7i]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M7I FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</scene>, <scene name='pdbligand=PRD_001063:Beta-Hairpin+Peptidomimetic+antibiotic+TWL(DAB)(ORN)(DLY)RW(ORN)(DAB)AK(DPR)P'>PRD_001063</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m7j|2m7j]]</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=2m7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m7i OCA], [https://pdbe.org/2m7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m7i RCSB], [https://www.ebi.ac.uk/pdbsum/2m7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m7i ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2m7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m7i OCA], [http://pdbe.org/2m7i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m7i RCSB], [http://www.ebi.ac.uk/pdbsum/2m7i PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Moehle, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Robinson, J]] | + | [[Category: Moehle K]] |
| - | [[Category: Schmidt, J]] | + | [[Category: Robinson J]] |
| - | [[Category: Antibiotic]] | + | [[Category: Schmidt J]] |
| - | [[Category: Beta-hairpin]]
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| - | [[Category: Peptidomimetic]]
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| Structural highlights
Publication Abstract from PubMed
We report structural studies in aqueous solution on backbone cyclic peptides that possess potent antimicrobial activity specifically against Pseudomonas sp. The peptides target the beta-barrel outer membrane protein LptD, which plays an essential role in lipopolysaccharide transport to the outer membrane. The peptide L27-11 contains a 12-residue loop (T(1)W(2)L(3)K(4)K(5)R(6)R(7)W(8)K(9)K(10)A(11)K(12)) linked to a DPro-LPro template. Two related peptides were also studied, one with various Lys to ornithine or diaminobutyric acid substitutions as well as a DLys(6) (called LB-01), and another containing the same loop sequence, but linked to an LPro-DPro template (called LB-02). NMR studies and MD simulations show that L27-11 and LB-01 adopt beta-hairpin structures in solution. In contrast, LB-02 is more flexible and importantly, adopts a wide variety of different backbone conformations, but not beta-hairpin conformations. L27-11 and LB-01 show antimicrobial activity in the nanomolar range against Pseudomonas aeruginosa, whereas LB-02 is essentially inactive. Thus the beta-hairpin structure of the peptide is important for antimicrobial activity. An alanine scan of L27-11 revealed that tryptophan side chains (W(2)/W(8)) displayed on opposite faces of the beta-hairpin represent key groups contributing to antimicrobial activity.
Structural studies of beta-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp.,Schmidt J, Patora-Komisarska K, Moehle K, Obrecht D, Robinson JA Bioorg Med Chem. 2013 Sep 15;21(18):5806-10. doi: 10.1016/j.bmc.2013.07.013. Epub, 2013 Jul 17. PMID:23932450[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schmidt J, Patora-Komisarska K, Moehle K, Obrecht D, Robinson JA. Structural studies of beta-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp. Bioorg Med Chem. 2013 Sep 15;21(18):5806-10. doi: 10.1016/j.bmc.2013.07.013. Epub, 2013 Jul 17. PMID:23932450 doi:10.1016/j.bmc.2013.07.013
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