5dm0

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==Crystal structure of the plantazolicin methyltransferase BamL in complex with triazolic desmethylPZN analog and SAH==
==Crystal structure of the plantazolicin methyltransferase BamL in complex with triazolic desmethylPZN analog and SAH==
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<StructureSection load='5dm0' size='340' side='right' caption='[[5dm0]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
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<StructureSection load='5dm0' size='340' side='right'caption='[[5dm0]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5dm0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacvz Bacvz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DM0 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5dm0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_velezensis_FZB42 Bacillus velezensis FZB42]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DM0 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5D8:ETHYL+2-(2-{2-[(1S)-1-AMINO-4-CARBAMIMIDAMIDOBUTYL]-1,3-THIAZOL-4-YL}-5-METHYL-1,3-OXAZOL-4-YL)-1,3-THIAZOLE-4-CARBOXYLATE'>5D8</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dly|5dly]], [[5dm1|5dm1]], [[5dm2|5dm2]], [[5dm4|5dm4]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5D8:ETHYL+2-(2-{2-[(1S)-1-AMINO-4-CARBAMIMIDAMIDOBUTYL]-1,3-THIAZOL-4-YL}-5-METHYL-1,3-OXAZOL-4-YL)-1,3-THIAZOLE-4-CARBOXYLATE'>5D8</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RBAM_007500 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=326423 BACVZ])</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=5dm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dm0 OCA], [https://pdbe.org/5dm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dm0 RCSB], [https://www.ebi.ac.uk/pdbsum/5dm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dm0 ProSAT]</span></td></tr>
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<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=5dm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dm0 OCA], [http://pdbe.org/5dm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dm0 RCSB], [http://www.ebi.ac.uk/pdbsum/5dm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dm0 ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/A7Z2A9_BACVZ A7Z2A9_BACVZ]
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Peptide antibiotics represent a class of conformationally constrained natural products of growing pharmaceutical interest. Plantazolicin (PZN) is a linear, polyheterocyclic natural product with highly selective and potent activity against the anthrax-causing bacterium, Bacillus anthracis. The bioactivity of PZN is contingent on dimethylation of its N-terminal Arg residue by an S-adenosylmethionine-dependent methyltransferase. Here, we explore the substrate tolerances of two homologous PZN methyltransferases by carrying out kinetic analyses of the enzymes against a synthetic panel of truncated PZN analogs containing the N-terminal Arg residue. X-ray cocrystal structures of the PZN methyltransferases with each of these heterocycle-containing substrates provide a rationale for understanding the strict substrate specificity of these enzymes. Kinetic studies of structure-guided, site-specific variants allowed for the assignment of residues governing catalysis and substrate scope. Microbiological testing further revealed that upon dimethylation of the N-terminal Arg, a pentaheterocyclized PZN analog retained potent anti-B. anthracis activity, nearly equal to that of full-length PZN. These studies may be useful in the biosynthetic engineering of natural product analogs with different bioactivity profiles, as demonstrated by our identification of a truncated plantazolicin derivative that is active against methicillin-resistant Staphylococcus aureus (MRSA).
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Insights into methyltransferase specificity and bioactivity of derivatives of the antibiotic plantazolicin.,Hao Y, Blair PM, Sharma A, Mitchell DA, Nair SK ACS Chem Biol. 2015 May 15;10(5):1209-1216. doi: 10.1021/cb501042a. Epub 2015 Feb, 11. PMID:25635336<ref>PMID:25635336</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5dm0" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacvz]]
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[[Category: Bacillus velezensis FZB42]]
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[[Category: Hao, Y]]
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[[Category: Large Structures]]
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[[Category: Nair, S K]]
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[[Category: Hao Y]]
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[[Category: Desmethylpzn analog]]
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[[Category: Nair SK]]
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[[Category: N-methyltransferase]]
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[[Category: Plantazolicin]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal structure of the plantazolicin methyltransferase BamL in complex with triazolic desmethylPZN analog and SAH

PDB ID 5dm0

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