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| | ==NMR STRUCTURE OF THE LANTIBIOTIC ACTAGARDINE== | | ==NMR STRUCTURE OF THE LANTIBIOTIC ACTAGARDINE== |
| - | <StructureSection load='1aj1' size='340' side='right'caption='[[1aj1]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='1aj1' size='340' side='right'caption='[[1aj1]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1aj1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinoplanes_liguriensis Actinoplanes liguriensis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AJ1 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1aj1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinoplanes_liguriensis Actinoplanes liguriensis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AJ1 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene>, <scene name='pdbligand=PRD_000194:ACTAGARDINE'>PRD_000194</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1mqx|1mqx]], [[1mqy|1mqy]], [[1mqz|1mqz]], [[1qow|1qow]], [[1w9n|1w9n]], [[1wco|1wco]], [[2dde|2dde]], [[2ktn|2ktn]], [[2kto|2kto]]</div></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1aj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aj1 OCA], [https://pdbe.org/1aj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1aj1 RCSB], [https://www.ebi.ac.uk/pdbsum/1aj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1aj1 ProSAT]</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=1aj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aj1 OCA], [https://pdbe.org/1aj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1aj1 RCSB], [https://www.ebi.ac.uk/pdbsum/1aj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1aj1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LANA_ACTGA LANA_ACTGA] Has potent antibacterial activity against some Gram-positive bacteria (PubMed:19400806). Has good antistreptococcal activity. Inhibits cell wall biosynthesis by binding to lipid II and blocking transglycosylation (PubMed:9449277).<ref>PMID:19400806</ref> <ref>PMID:9449277</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Actinoplanes liguriensis]] | | [[Category: Actinoplanes liguriensis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jung, G]] | + | [[Category: Jung G]] |
| - | [[Category: Zimmermann, N]] | + | [[Category: Zimmermann N]] |
| - | [[Category: Antibiotic]]
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| - | [[Category: Antimicrobial]]
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| - | [[Category: Bacteriocin]]
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| - | [[Category: Lantibiotic]]
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| - | [[Category: Thioester]]
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| - | [[Category: Transmembrane pore]]
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| Structural highlights
Function
LANA_ACTGA Has potent antibacterial activity against some Gram-positive bacteria (PubMed:19400806). Has good antistreptococcal activity. Inhibits cell wall biosynthesis by binding to lipid II and blocking transglycosylation (PubMed:9449277).[1] [2]
Publication Abstract from PubMed
The three-dimensional solution structure of the lantibiotic actagardine was determined at high resolution by homonuclear and heteronuclear two-dimensional and three-dimensional NMR spectroscopy in [2H3]acetonitrile/H2O (7:3). 133 non-trivial distance and 22 torsional-angle constraints were derived from the NMR data. An ensemble of 15 low-energy structures was calculated by distance geometry followed by an iterative relaxation-matrix-refinement procedure. The rmsd of the backbone coordinates with respect to the average structure was 17 pm. The two distinct thioether ring systems 1-6 and 7-19 were even better defined, with backbone rmsd of 10 pm and 14 pm, respectively. Actagardine shows a rigid compact globular shape based on the constraining bridging pattern, which is composed of an N-terminal lanthionine ring from residues 1-6 and three intertwined C-terminal methyllanthionine rings comprising residues 7-12, 9-17 and 14-19. In addition, this C-terminal ring system is stabilised by a short antiparallel beta sheet. A feature of the actagardine structure is the presence of two putative binding pockets. A pocket is generated by the covalent constraints of the C-terminal thioether ring system. The rim of this pocket is built up by a loop structure comprising residues 12-19, whose backbone amide protons are all directed to the centre of the pocket. The second pocket is formed by an L-shaped orientation of the N-terminal and C-terminal thioether ring systems. The only two hydrophilic amino acid residues of actagardine, Glu11 and Ser2, are directed to this pocket. A region of high sequence similarity with the related lantibiotic mersacidin is located exactly at the position of the second pocket (residues 3-12). This suggests that the second pocket is responsible for the antibiotic mode of action of actagardine and mersacidin as inhibitors of the murein biosynthesis of gram-positive bacteria.
The three-dimensional solution structure of the lantibiotic murein-biosynthesis-inhibitor actagardine determined by NMR.,Zimmermann N, Jung G Eur J Biochem. 1997 Jun 15;246(3):809-19. PMID:9219543[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Boakes S, Cortés J, Appleyard AN, Rudd BA, Dawson MJ. Organization of the genes encoding the biosynthesis of actagardine and engineering of a variant generation system. Mol Microbiol. 2009 Jun;72(5):1126-36. PMID:19400806 doi:10.1111/j.1365-2958.2009.06708.x
- ↑ Brötz H, Bierbaum G, Leopold K, Reynolds PE, Sahl HG. The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II. Antimicrob Agents Chemother. 1998 Jan;42(1):154-60. PMID:9449277 doi:10.1128/AAC.42.1.154
- ↑ Zimmermann N, Jung G. The three-dimensional solution structure of the lantibiotic murein-biosynthesis-inhibitor actagardine determined by NMR. Eur J Biochem. 1997 Jun 15;246(3):809-19. PMID:9219543
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