View source for 8czl


==Human LanCL1 bound to methyl glutathione (MeGSH)==
<StructureSection load='8czl' size='340' side='right'caption='[[8czl]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8czl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CZL 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]] 1.58&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSM:L-GAMMA-GLUTAMYL-S-METHYLCYSTEINYLGLYCINE'>GSM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8czl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8czl OCA], [https://pdbe.org/8czl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8czl RCSB], [https://www.ebi.ac.uk/pdbsum/8czl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8czl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LANC1_HUMAN LANC1_HUMAN] May play a role in EPS8 signaling. Binds glutathion.<ref>PMID:19528316</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In both eukarya and bacteria, the addition of Cys to dehydroalanine (Dha) and dehydrobutyrine (Dhb) occurs in various biological processes. In bacteria, intramolecular thia-Michael addition catalyzed by lanthipeptide cyclases (LanC) proteins or protein domains gives rise to a class of natural products called lanthipeptides. In eukarya, dehydroamino acids in signaling proteins are introduced by effector proteins produced by pathogens like Salmonella to dysregulate host defense mechanisms. A eukaryotic LanC-like (LanCL) enzyme catalyzes the addition of Cys in glutathione to Dha/Dhb to protect the cellular proteome from unwanted chemical and biological activity. To date, the mechanism of the enzyme-catalyzed thia-Michael addition has remained elusive. We report here the crystal structures of the human LanCL1 enzyme complexed with different ligands, including the product of thia-Michael addition of glutathione to a Dhb-containing peptide that represents the activation loop of Erk. The structures show that a zinc ion activates the Cys thiolate for nucleophilic attack and that a conserved His is poised to protonate the enolate intermediate to achieve a net anti-addition. A second His hydrogen bonds to the carbonyl oxygen of the former Dhb and may stabilize the negative charge that builds up on this oxygen atom in the enolate intermediate. Surprisingly, the latter His is not conserved in orthologous enzymes that catalyze thia-Michael addition to Dha/Dhb. Eukaryotic LanCLs contain a His, whereas bacterial stand-alone LanCs have a Tyr residue, and LanM enzymes that have LanC-like domains have a Lys, Asn, or His residue. Mutational and binding studies support the importance of these residues for catalysis.

The mechanism of thia-Michael addition catalyzed by LanC enzymes.,Ongpipattanakul C, Liu S, Luo Y, Nair SK, van der Donk WA Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2217523120. doi: , 10.1073/pnas.2217523120. Epub 2023 Jan 12. PMID:36634136<ref>PMID:36634136</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8czl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Nair SK]]
[[Category: Ongpipattanakul C]]