4v2p: Difference between revisions
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==Ketosynthase MxnB== | |||
<StructureSection load='4v2p' size='340' side='right'caption='[[4v2p]], [[Resolution|resolution]] 1.67Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4v2p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Myxococcus_fulvus Myxococcus fulvus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V2P FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=4v2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v2p OCA], [https://pdbe.org/4v2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v2p RCSB], [https://www.ebi.ac.uk/pdbsum/4v2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v2p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/T1SF45_MYXFU T1SF45_MYXFU] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Myxopyronins are alpha-pyrone antibiotics produced by the terrestrial bacterium Myxococcus fulvus Mx f50 and possess antibacterial activity against Gram-positive and Gram-negative pathogens. They target the bacterial RNA polymerase (RNAP) "switch region" as non-competitive inhibitors and display no cross-resistance to the established RNAP inhibitor rifampicin. Recent analysis of the myxopyronin biosynthetic pathway led to the hypothesis that this secondary metabolite is produced from two separate polyketide parts, which are condensed by the stand-alone ketosynthase MxnB. Using in vitro assays we show that MxnB catalyzes a unique condensation reaction forming the alpha-pyrone ring of myxopyronins from two activated acyl chains in form of their beta-keto intermediates. MxnB is able to accept thioester substrates coupled to either N-acetylcysteamine (NAC) or a specific carrier protein (CP). The turnover rate of MxnB for substrates bound to CP was 12-fold higher than for NAC substrates, demonstrating the importance of protein-protein interactions in polyketide synthase (PKS) systems. The crystal structure of MxnB reveals the enzyme to be an unusual member of the ketosynthase group capable of binding and condensing two long alkyl chains bound to carrier proteins. The geometry of the two binding tunnels supports the biochemical data and allows us to propose an order of reaction, which is supported by the identification of novel myxopyronin congeners in the extract of the producer strain. Insights into the mechanism of this unique condensation reaction do not only expand our knowledge regarding the thiolase enzyme family but also opens up opportunities for PKS bioengineering to achieve directed structural modifications. | |||
In vitro reconstitution of alpha-pyrone ring formation in myxopyronin biosynthesis.,Sucipto H, Sahner JH, Prusov E, Wenzel SC, Hartmann RW, Koehnke J, Muller R Chem Sci. 2015 Aug 1;6(8):5076-5085. doi: 10.1039/c5sc01013f. Epub 2015 May 18. PMID:29308173<ref>PMID:29308173</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4v2p" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Myxococcus fulvus]] | |||
[[Category: Koehnke J]] | |||