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| | ==NMR solution structure of type-B lantibiotics mersacidin in DPC micelles== | | ==NMR solution structure of type-B lantibiotics mersacidin in DPC micelles== |
| - | <StructureSection load='1mqy' size='340' side='right' caption='[[1mqy]], [[NMR_Ensembles_of_Models | 13 NMR models]]' scene=''> | + | <StructureSection load='1mqy' size='340' side='right'caption='[[1mqy]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1mqy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacsy Bacsy]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MQY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MQY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1mqy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_sp._HIL-Y85/54728 Bacillus sp. HIL-Y85/54728]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MQY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MQY FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene>, <scene name='pdbligand=DHA:2-AMINO-ACRYLIC+ACID'>DHA</scene>, <scene name='pdbligand=TEE:2-AMINO-ETHENETHIOL'>TEE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1aj1|1aj1]], [[1mqx|1mqx]], [[1mqz|1mqz]], [[1qow|1qow]], [[1w9n|1w9n]], [[1wco|1wco]], [[2dde|2dde]], [[2ktn|2ktn]], [[2kto|2kto]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene>, <scene name='pdbligand=DHA:2-AMINO-ACRYLIC+ACID'>DHA</scene>, <scene name='pdbligand=PRD_000199:Mersacidin'>PRD_000199</scene>, <scene name='pdbligand=TEE:2-AMINO-ETHENETHIOL'>TEE</scene></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=1mqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mqy OCA], [http://pdbe.org/1mqy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mqy RCSB], [http://www.ebi.ac.uk/pdbsum/1mqy PDBsum]</span></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=1mqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mqy OCA], [https://pdbe.org/1mqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mqy RCSB], [https://www.ebi.ac.uk/pdbsum/1mqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mqy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MRSA_BACSY MRSA_BACSY]] Kills a number of Gram-positive bacteria. Acts at the level of cell wall biosynthesis by interfering with bacterial peptidoglycan biosynthesis. Specifically inhibits the conversion of the lipid II intermediate into polymeric nascent glycan strands by transglycosylation. May interact with the peptidoglycan precursor rather than with the enzyme. | + | [https://www.uniprot.org/uniprot/MRSA_BACSY MRSA_BACSY] Kills a number of Gram-positive bacteria. Acts at the level of cell wall biosynthesis by interfering with bacterial peptidoglycan biosynthesis. Specifically inhibits the conversion of the lipid II intermediate into polymeric nascent glycan strands by transglycosylation. May interact with the peptidoglycan precursor rather than with the enzyme. |
| | <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: Bacsy]] | + | [[Category: Bacillus sp. HIL-Y85/54728]] |
| - | [[Category: Bierbaum, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Bonvin, A M]] | + | [[Category: Bierbaum G]] |
| - | [[Category: Breukink, E]] | + | [[Category: Bonvin AM]] |
| - | [[Category: Hsu, S T]] | + | [[Category: Breukink E]] |
| - | [[Category: Kaptein, R]] | + | [[Category: Hsu S-T]] |
| - | [[Category: Kruijff, B de]]
| + | [[Category: Kaptein R]] |
| - | [[Category: Nuland, N A.van]]
| + | [[Category: Sahl H-G]] |
| - | [[Category: Sahl, H G]] | + | [[Category: De Kruijff B]] |
| - | [[Category: Antibiotic]] | + | [[Category: Van Nuland NA]] |
| - | [[Category: Antimicrobial]] | + | |
| - | [[Category: Bacteriocin]]
| + | |
| - | [[Category: Lantibiotic]]
| + | |
| - | [[Category: Peptidoglycan methicillin resistance]]
| + | |
| - | [[Category: Thioester]]
| + | |
| Structural highlights
Function
MRSA_BACSY Kills a number of Gram-positive bacteria. Acts at the level of cell wall biosynthesis by interfering with bacterial peptidoglycan biosynthesis. Specifically inhibits the conversion of the lipid II intermediate into polymeric nascent glycan strands by transglycosylation. May interact with the peptidoglycan precursor rather than with the enzyme.
Publication Abstract from PubMed
Mersacidin belongs to the type B lantibiotics (lanthionine-containing antibiotics) that contain post-translationally modified amino acids and cyclic ring structures. It targets the cell wall precursor lipid II and thereby inhibits cell wall synthesis. In light of the emerging antibiotics resistance problem, the understanding of the antibacterial activity on a structural basis provides a key to circumvent this issue. Here we present solution NMR studies of mersacidin-lipid II interaction in dodecylphosphocholine (DPC) micelles. Distinct solution structures of mersacidin were determined in three different states: in water/methanol solution and in DPC micelles with and without lipid II. The structures in various sample conditions reveal remarkable conformational changes in which the junction between Ala-12 and Abu-13 (where Abu is aminobutyric acid) effectively serves as the hinge for the opening and closure of the ring structures. The DPC micelle-bound form resembles the previously determined NMR and x-ray crystal structures of mersacidin in pure methanol but substantially deviates from the other two states in our current report. The structural changes delineate the large chemical shift perturbations observed during the course of a two-step (15)N-(1)H heteronuclear single quantum coherence titration. They also modulate the surface charge distribution of mersacidin suggesting that electrostatics play a central role in the mersacidin-lipid II interaction. The observed conformational adaptability of mersacidin might be a general feature of lipid II-interacting antibiotics/peptides.
NMR study of mersacidin and lipid II interaction in dodecylphosphocholine micelles. Conformational changes are a key to antimicrobial activity.,Hsu ST, Breukink E, Bierbaum G, Sahl HG, de Kruijff B, Kaptein R, van Nuland NA, Bonvin AM J Biol Chem. 2003 Apr 11;278(15):13110-7. Epub 2003 Jan 31. PMID:12562773[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hsu ST, Breukink E, Bierbaum G, Sahl HG, de Kruijff B, Kaptein R, van Nuland NA, Bonvin AM. NMR study of mersacidin and lipid II interaction in dodecylphosphocholine micelles. Conformational changes are a key to antimicrobial activity. J Biol Chem. 2003 Apr 11;278(15):13110-7. Epub 2003 Jan 31. PMID:12562773 doi:10.1074/jbc.M211144200
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