View source for 5txe


==AtxE2 Isopeptidase - S527A Variant with Astexin3-dC4 Bound==
<StructureSection load='5txe' size='340' side='right'caption='[[5txe]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5txe]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Asticcacaulis_excentricus_CB_48 Asticcacaulis excentricus CB 48]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TXE 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]] 2.2&#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=5txe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txe OCA], [https://pdbe.org/5txe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5txe RCSB], [https://www.ebi.ac.uk/pdbsum/5txe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5txe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATXE2_ASTEC ATXE2_ASTEC] Lasso peptide isopeptidase that specifically hydrolyzes Astexin-2 and Astexin-3, converting them to linear peptides (PubMed:23862624). Has only a few specific contacts with substrates, because it recognizes Astexin knotted structure (principally the loop structure) (PubMed:26534965, PubMed:27998080). Its binding to lasso peptides opens them to expose the isopeptide bonds for hydrolysis (PubMed:27998080).<ref>PMID:23862624</ref> <ref>PMID:26534965</ref> <ref>PMID:27998080</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lasso peptides are a class of bioactive ribosomally synthesized and post-translationally modified peptides (RiPPs), with a threaded knot structure that is formed by an isopeptide bond attaching the N-terminus of the peptide to a side chain carboxylate. Some lasso peptide biosynthetic clusters harbor an enzyme that specifically hydrolyzes the isopeptide bond to yield the linear peptide. We describe here the 2.4 A resolution structure of a lasso peptide isopeptidase revealing a topologically novel didomain architecture consisting of an open beta-propeller appended to an alpha/beta hydrolase domain. The 2.2 A resolution cocrystal structure of an inactive variant in complex with a lasso peptide reveals deformation of the substrate, and reorganization of the enzyme active site, which exposes and orients the isopeptide bond for hydrolysis. Structure-based mutational analysis reveals how this enzyme recognizes the lasso peptide substrate by shape complementarity rather than through sequence specificity. The isopeptidase gene can be used to facilitate genome mining, as a network-based mining strategy queried with this sequence identified 87 putative lasso peptide biosynthetic clusters, 65 of which have not been previously described. Lastly, we validate this mining approach by heterologous expression of two clusters encoded within the genome of Asticcaucalis benevestitus, and demonstrate that both clusters produce lasso peptides.

Structure of the Lasso Peptide Isopeptidase Identifies a Topology for Processing Threaded Substrates.,Chekan JR, Koos JD, Zong C, Maksimov MO, Link AJ, Nair SK J Am Chem Soc. 2016 Dec 21;138(50):16452-16458. doi: 10.1021/jacs.6b10389. Epub, 2016 Dec 7. PMID:27998080<ref>PMID:27998080</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5txe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Asticcacaulis excentricus CB 48]]
[[Category: Large Structures]]
[[Category: Chekan JR]]
[[Category: Nair SK]]