View source for 7bza


==Template lasso peptide C24==
<StructureSection load='7bza' size='340' side='right'caption='[[7bza]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7bza]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BZA FirstGlance]. <br>
</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=7bza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bza OCA], [https://pdbe.org/7bza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bza RCSB], [https://www.ebi.ac.uk/pdbsum/7bza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bza ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Lasso peptides are a unique family of natural products whose structures feature a specific threaded fold, which confers these peptides the resistance to thermal and proteolytic degradation. This stability gives lasso peptides excellent pharmacokinetic properties, which together with their diverse reported bioactivities have garnered extensive attention because of their drug development potential. Notably, the threaded fold has proven quite inaccessible by chemical synthesis, which has hindered efficient generation of structurally diverse lasso peptides. We herein report the discovery of a new lasso peptide stlassin (1) by gene activation based on a Streptomyces heterologous expression system. Site-directed mutagenesis on the precursor peptide-encoding gene is carried out systematically, generating 17 stlassin derivatives (2-17 and 21) with residue-replacements at specific positions of 1. The solution NMR structures of 1, 3, 4, 14 and 16 are determined, supporting structural comparisons that ultimately enabled the rational production of disulfide bond-containing derivatives 18 and 19, whose structures do not belong to any of the four classes currently used to classify lasso peptides. Several site-selective chemical modifications are first applied on 16 and 21, efficiently generating new derivatives (20, 22-27) whose structures bear various decorations beyond the peptidyl monotonicity. The high production yields of these stlassin derivatives facilitate biological assays, which show that 1, 4, 16, 20, 21 and 24 possess antagonistic activities against the binding of lipopolysaccharides to toll-like receptor 4 (TLR4). These results demonstrate proof-of-concept for the combined mutational/chemical generation of lasso peptide libraries to support drug lead development.

Rational generation of lasso peptides based on biosynthetic gene mutations and site-selective chemical modifications.,Liu T, Ma X, Yu J, Yang W, Wang G, Wang Z, Ge Y, Song J, Han H, Zhang W, Yang D, Liu X, Ma M Chem Sci. 2021 Aug 10;12(37):12353-12364. doi: 10.1039/d1sc02695j. eCollection, 2021 Sep 29. PMID:34603665<ref>PMID:34603665</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7bza" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp]]
[[Category: Liu T]]
[[Category: Liu XH]]
[[Category: Ma M]]
[[Category: Ma XJ]]
[[Category: Yang DH]]
[[Category: Yu JH]]