View source for 5ups


==Acyl-CoA synthetase PtmA2 from Streptomyces platensis in complex with SBNP663 ligand==
<StructureSection load='5ups' size='340' side='right'caption='[[5ups]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ups]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"streptomyces_platensis_subsp._rosaceus"_karwowski_et_al._1994 "streptomyces platensis subsp. rosaceus" karwowski et al. 1994]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UPS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UPS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8K1:5-O-[(R)-HYDROXY{[(7BETA,8ALPHA,9BETA,10ALPHA,11BETA,13ALPHA)-7-HYDROXY-19-OXO-11,16-EPOXYKAURAN-19-YL]OXY}PHOSPHORYL]ADENOSINE'>8K1</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5e7q|5e7q]], [[5upq|5upq]], [[5upt|5upt]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ups FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ups OCA], [http://pdbe.org/5ups PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ups RCSB], [http://www.ebi.ac.uk/pdbsum/5ups PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ups ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Acyl-coenzyme A (CoA) ligases catalyze the activation of carboxylic acids via a two-step reaction of adenylation followed by thioesterification. Here, we report the discovery of a non-adenylating acyl-CoA ligase PtmA2 and the functional separation of an acyl-CoA ligase reaction. Both PtmA1 and PtmA2, two acyl-CoA ligases from the biosynthetic pathway of platensimycin and platencin, are necessary for the two steps of CoA activation. Gene inactivation of ptmA1 and ptmA2 resulted in the accumulation of free acid and adenylate intermediates, respectively. Enzymatic and structural characterization of PtmA2 confirmed its ability to only catalyze thioesterification. Structural characterization of PtmA2 revealed it binds both free acid and adenylate substrates and undergoes the established mechanism of domain alternation. Finally, site-directed mutagenesis restored both the adenylation and complete CoA activation reactions. This study challenges the currently accepted paradigm of adenylating enzymes and inspires future investigations on functionally separated acyl-CoA ligases and their ramifications in biology.

Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme.,Wang N, Rudolf JD, Dong LB, Osipiuk J, Hatzos-Skintges C, Endres M, Chang CY, Babnigg G, Joachimiak A, Phillips GN Jr, Shen B Nat Chem Biol. 2018 Jul;14(7):730-737. doi: 10.1038/s41589-018-0061-0. Epub 2018 , Jun 4. PMID:29867143<ref>PMID:29867143</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ups" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Streptomyces platensis subsp. rosaceus karwowski et al. 1994]]
[[Category: Large Structures]]
[[Category: Babnigg, G]]
[[Category: Chang, C Y]]
[[Category: Endres, M]]
[[Category: Hatzos-Skintges, C]]
[[Category: Joachimiak, A]]
[[Category: Structural genomic]]
[[Category: Ma, M]]
[[Category: NatPro, Enzyme Discovery for Natural Product Biosynthesis]]
[[Category: Osipiuk, J]]
[[Category: Phillips, G N]]
[[Category: Rudolf, J D]]
[[Category: Shen, B]]
[[Category: Acyl-coa synthetase]]
[[Category: Apc109894]]
[[Category: Enzyme discovery for natural product biosynthesis]]
[[Category: Mcsg]]
[[Category: Natpro]]
[[Category: Psi-biology]]
[[Category: Ptma2]]
[[Category: Transferase]]