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The | ==E. coli Microcin synthetase McbBCD complex with pro-MccB17 bound== | ||
<StructureSection load='6gos' size='340' side='right' caption='[[6gos]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6gos]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_mg1655 Escherichia coli mg1655]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GOS FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=F6N:'>F6N</scene>, <scene name='pdbligand=F75:'>F75</scene>, <scene name='pdbligand=OTZ:'>OTZ</scene>, <scene name='pdbligand=TOZ:'>TOZ</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mcbA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=511145 Escherichia coli MG1655]), mcbB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=511145 Escherichia coli MG1655]), mcbC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=511145 Escherichia coli MG1655]), mcbD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=511145 Escherichia coli MG1655])</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=6gos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gos OCA], [http://pdbe.org/6gos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gos RCSB], [http://www.ebi.ac.uk/pdbsum/6gos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gos ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/MCBD_ECOLX MCBD_ECOLX]] Necessary to process the inactive microcin B17 (McbA) precursor into the active peptide. [[http://www.uniprot.org/uniprot/MCBA_ECOLX MCBA_ECOLX]] This glycine-rich peptide antibiotic inhibits DNA replication in many enteric bacteria, that leads to induction of the SOS repair system, massive DNA degradation and cell death. B17 inhibits type II topoisomerase by trapping an enzyme - DNA cleavable complex.<ref>PMID:1846808</ref> [[http://www.uniprot.org/uniprot/MCBC_ECOLX MCBC_ECOLX]] Necessary to process the inactive microcin B17 (McbA) precursor into the active peptide. [[http://www.uniprot.org/uniprot/MCBB_ECOLX MCBB_ECOLX]] Necessary to process the inactive microcin B17 (McbA) precursor into the active peptide. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The introduction of azole heterocycles into a peptide backbone is the principal step in the biosynthesis of numerous compounds with therapeutic potential. One of them is microcin B17, a bacterial topoisomerase inhibitor whose activity depends on the conversion of selected serine and cysteine residues of the precursor peptide to oxazoles and thiazoles by the McbBCD synthetase complex. Crystal structures of McbBCD reveal an octameric B4C2D2 complex with two bound substrate peptides. Each McbB dimer clamps the N-terminal recognition sequence, while the C-terminal heterocycle of the modified peptide is trapped in the active site of McbC. The McbD and McbC active sites are distant from each other, which necessitates alternate shuttling of the peptide substrate between them, while remaining tethered to the McbB dimer. An atomic-level view of the azole synthetase is a starting point for deeper understanding and control of biosynthesis of a large group of ribosomally synthesized natural products. | |||
Architecture of Microcin B17 Synthetase: An Octameric Protein Complex Converting a Ribosomally Synthesized Peptide into a DNA Gyrase Poison.,Ghilarov D, Stevenson CEM, Travin DY, Piskunova J, Serebryakova M, Maxwell A, Lawson DM, Severinov K Mol Cell. 2019 Jan 16. pii: S1097-2765(18)31002-5. doi:, 10.1016/j.molcel.2018.11.032. PMID:30661981<ref>PMID:30661981</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 6gos" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli mg1655]] | |||
[[Category: Ghilarov, D]] | [[Category: Ghilarov, D]] | ||
[[Category: | [[Category: Lawson, D M]] | ||
[[Category: Maxwell, A]] | [[Category: Maxwell, A]] | ||
[[Category: Piskunova, J]] | |||
[[Category: Serebryakova, M]] | |||
[[Category: Severinov, K]] | [[Category: Severinov, K]] | ||
[[Category: | [[Category: Stevenson, C E.M]] | ||
[[Category: Travin, D | [[Category: Travin, D Y]] | ||
[[Category: | [[Category: Antibiotic-inhibitor complex]] | ||
[[Category: Biosynthetic protein]] | |||
[[Category: Dna gyrase]] | |||
[[Category: Heterocyclization]] | |||
[[Category: Microcin]] | |||
[[Category: Posttranslational modification]] | |||