View source for 8wgo


==Cryo-EM structure of ClassIII Lanthipeptide modification enzyme PneKC in the presence of PneA and GTPrS.==
<StructureSection load='8wgo' size='340' side='right'caption='[[8wgo]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8wgo]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8WGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WGO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#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=8wgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wgo OCA], [https://pdbe.org/8wgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wgo RCSB], [https://www.ebi.ac.uk/pdbsum/8wgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wgo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A2U3S0J5_STREE A0A2U3S0J5_STREE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Naturally occurring lanthipeptides, peptides post-translationally modified by various enzymes, hold significant promise as antibiotics. Despite extensive biochemical and structural studies, the events preceding peptide modification remain poorly understood. Here, we identify a distinct subclass of lanthionine synthetase KC (LanKC) enzymes with distinct structural and functional characteristics. We show that PneKC, a member of this subclass, forms a dimer and possesses GTPase activity. Through three cryo-EM structures of PneKC, we illustrate different stages of peptide PneA binding, from initial recognition to full binding. Our structures show the kinase domain complexed with the PneA core peptide and GTPgammaS, a phosphate-bound lyase domain, and an unconventional cyclase domain. The leader peptide of PneA interact with a gate loop, transitioning from an extended to a helical conformation. We identify a dimerization hot spot and propose a "negative cooperativity" mechanism toggling the enzyme between tense and relaxed conformation. Additionally, we identify an important salt bridge in the cyclase domain, differing from those in in conventional cyclase domains. These residues are highly conserved in the LanKC subclass and are part of two signature motifs. These results unveil potential differences in lanthipeptide modification enzymes assembly and deepen our understanding of allostery in these multifunctional enzymes.

Mechanistic insights into lanthipeptide modification by a distinct subclass of LanKC enzyme that forms dimers.,Li Y, Shao K, Li Z, Zhu K, Gan BK, Shi J, Xiao Y, Luo M Nat Commun. 2024 Aug 17;15(1):7090. doi: 10.1038/s41467-024-51600-6. PMID:39154050<ref>PMID:39154050</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8wgo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pneumoniae]]
[[Category: Li J]]
[[Category: Li Y]]
[[Category: Luo M]]
[[Category: Shao K]]