View source for 9fcq


==CysG(N-16)-H122A mutant in complex with SAH from Kitasatospora cystarginea==
<StructureSection load='9fcq' size='340' side='right'caption='[[9fcq]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9fcq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Kitasatospora_cystarginea Kitasatospora cystarginea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FCQ 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]] 1.4&#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=9fcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fcq OCA], [https://pdbe.org/9fcq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fcq RCSB], [https://www.ebi.ac.uk/pdbsum/9fcq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fcq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A1W6R556_9ACTN A0A1W6R556_9ACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cystargolides and belactosins are natural products with a distinct dipeptide structure and an electrophilic beta-lactone warhead. They are known to inhibit proteases such as the proteasome or caseinolytic protease P, highlighting their potential in treating cancers and neurodegenerative diseases. Recent genetic analyses have shown homology between the biosynthetic pathways of the two inhibitors. Here, we characterize the O-methyltransferases BelI and CysG, which catalyze the initial step of beta-lactone formation. Employing techniques such as crystallography, computational analysis, mutagenesis, and activity assays, we identified a His-His-Asp (HHD) motif in the active sites of the two enzymes, which is crucial for binding a catalytically active calcium ion. Our findings thus elucidate a conserved divalent metal-dependent mechanism in both biosynthetic pathways that distinguishes BelI and CysG from previously characterized O-methyltransferases.

Deciphering the SAM- and Metal-Dependent Mechanism of O-Methyltransferases in Cystargolide and Belactosin Biosynthesis: A Structure-Activity Relationship Study.,Kuttenlochner W, Beller P, Kaysser L, Groll M J Biol Chem. 2024 Aug 7:107646. doi: 10.1016/j.jbc.2024.107646. PMID:39121999<ref>PMID:39121999</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9fcq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Kitasatospora cystarginea]]
[[Category: Large Structures]]
[[Category: Beller P]]
[[Category: Groll M]]
[[Category: Kaysser L]]
[[Category: Kuttenlochner W]]