3t5y: Difference between revisions
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< | ==Crystal structure of CerJ from Streptomyces tendae - malonic acid covalently linked to the catalytic Cystein C116== | ||
<StructureSection load='3t5y' size='340' side='right'caption='[[3t5y]], [[Resolution|resolution]] 2.12Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3t5y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/As_4.1460 As 4.1460]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T5Y FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MCS:MALONYL+CYSTEINE'>MCS</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;'>[[3s3l|3s3l]]</div></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=3t5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5y OCA], [https://pdbe.org/3t5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t5y RCSB], [https://www.ebi.ac.uk/pdbsum/3t5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t5y ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ketosynthases produce the carbon backbones of a vast number of biologically active polyketides by catalyzing Claisen condensations of activated acyl and malonyl building blocks. Here we report that a ketosynthase homolog from Streptomyces tendae, CerJ, unexpectedly forms malonyl esters during the biosynthesis of cervimycin, a glycoside antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). Deletion of cerJ yielded a substantially more active cervimycin variant lacking the malonyl side chain, and in vitro biotransformations revealed that CerJ is capable of transferring malonyl, methylmalonyl and dimethylmalonyl units onto the glycoside. According to phylogenetic analyses and elucidation of the crystal structure, CerJ is functionally and structurally positioned between the ketosynthase catalyzing Claisen condensations and acyl-ACP shuttles, and it features a noncanonical catalytic triad. Site-directed mutagenesis and structures of CerJ in complex with substrates not only allowed us to establish a model for the reaction mechanism but also provided insights into the evolution of this important subclass of the thiolase superfamily. | |||
A ketosynthase homolog uses malonyl units to form esters in cervimycin biosynthesis.,Bretschneider T, Zocher G, Unger M, Scherlach K, Stehle T, Hertweck C Nat Chem Biol. 2011 Dec 18. doi: 10.1038/nchembio.746. PMID:22179067<ref>PMID:22179067</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3t5y" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: As 4 1460]] | ||
[[Category: Large Structures]] | |||
[[Category: Bretschneider, T]] | |||
== | [[Category: Hertweck, C]] | ||
< | [[Category: Stehle, T]] | ||
[[Category: | [[Category: Zocher, G]] | ||
[[Category: Bretschneider, T | |||
[[Category: Hertweck, C | |||
[[Category: Stehle, T | |||
[[Category: Zocher, G | |||
[[Category: Fabh-like fold]] | [[Category: Fabh-like fold]] | ||
[[Category: O-malonyl transferase]] | [[Category: O-malonyl transferase]] | ||
[[Category: Thiloase superfamily]] | [[Category: Thiloase superfamily]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Latest revision as of 19:44, 6 July 2022
Crystal structure of CerJ from Streptomyces tendae - malonic acid covalently linked to the catalytic Cystein C116Crystal structure of CerJ from Streptomyces tendae - malonic acid covalently linked to the catalytic Cystein C116
Structural highlights
Publication Abstract from PubMedKetosynthases produce the carbon backbones of a vast number of biologically active polyketides by catalyzing Claisen condensations of activated acyl and malonyl building blocks. Here we report that a ketosynthase homolog from Streptomyces tendae, CerJ, unexpectedly forms malonyl esters during the biosynthesis of cervimycin, a glycoside antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). Deletion of cerJ yielded a substantially more active cervimycin variant lacking the malonyl side chain, and in vitro biotransformations revealed that CerJ is capable of transferring malonyl, methylmalonyl and dimethylmalonyl units onto the glycoside. According to phylogenetic analyses and elucidation of the crystal structure, CerJ is functionally and structurally positioned between the ketosynthase catalyzing Claisen condensations and acyl-ACP shuttles, and it features a noncanonical catalytic triad. Site-directed mutagenesis and structures of CerJ in complex with substrates not only allowed us to establish a model for the reaction mechanism but also provided insights into the evolution of this important subclass of the thiolase superfamily. A ketosynthase homolog uses malonyl units to form esters in cervimycin biosynthesis.,Bretschneider T, Zocher G, Unger M, Scherlach K, Stehle T, Hertweck C Nat Chem Biol. 2011 Dec 18. doi: 10.1038/nchembio.746. PMID:22179067[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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