View source for 6ecb


==Vlm2 thioesterase domain wild type structure 1==
<StructureSection load='6ecb' size='340' side='right'caption='[[6ecb]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ecb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_tsusimaensis Streptomyces tsusimaensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ECB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ECB 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]] 1.7&#8491;</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=6ecb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ecb OCA], [https://pdbe.org/6ecb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ecb RCSB], [https://www.ebi.ac.uk/pdbsum/6ecb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ecb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q1PSF3_9ACTN Q1PSF3_9ACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Many enzymes catalyse reactions that proceed through covalent acyl-enzyme (ester or thioester) intermediates(1). These enzymes include serine hydrolases(2,3) (encoded by one per cent of human genes, and including serine proteases and thioesterases), cysteine proteases (including caspases), and many components of the ubiquitination machinery(4,5). Their important acyl-enzyme intermediates are unstable, commonly having half-lives of minutes to hours(6). In some cases, acyl-enzyme complexes can be stabilized using substrate analogues or active-site mutations but, although these approaches can provide valuable insight(7-10), they often result in complexes that are substantially non-native. Here we develop a strategy for incorporating 2,3-diaminopropionic acid (DAP) into recombinant proteins, via expansion of the genetic code(11). We show that replacing catalytic cysteine or serine residues of enzymes with DAP permits their first-step reaction with native substrates, allowing the efficient capture of acyl-enzyme complexes that are linked through a stable amide bond. For one of these enzymes, the thioesterase domain of valinomycin synthetase(12), we elucidate the biosynthetic pathway by which it progressively oligomerizes tetradepsipeptidyl substrates to a dodecadepsipeptidyl intermediate, which it then cyclizes to produce valinomycin. By trapping the first and last acyl-thioesterase intermediates in the catalytic cycle as DAP conjugates, we provide structural insight into how conformational changes in thioesterase domains of such nonribosomal peptide synthetases control the oligomerization and cyclization of linear substrates. The encoding of DAP will facilitate the characterization of diverse acyl-enzyme complexes, and may be extended to capturing the native substrates of transiently acylated proteins of unknown function.

Trapping biosynthetic acyl-enzyme intermediates with encoded 2,3-diaminopropionic acid.,Huguenin-Dezot N, Alonzo DA, Heberlig GW, Mahesh M, Nguyen DP, Dornan MH, Boddy CN, Schmeing TM, Chin JW Nature. 2018 Dec 12. pii: 10.1038/s41586-018-0781-z. doi:, 10.1038/s41586-018-0781-z. PMID:30542153<ref>PMID:30542153</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ecb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces tsusimaensis]]
[[Category: Alonzo DA]]
[[Category: Schmeing TM]]