View source for 9icz


==C-Methyltransferase SeMT from Saccharopolyspora erythraea==
<StructureSection load='9icz' size='340' side='right'caption='[[9icz]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9icz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharopolyspora_erythraea Saccharopolyspora erythraea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ICZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ICZ 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=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=9icz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9icz OCA], [https://pdbe.org/9icz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9icz RCSB], [https://www.ebi.ac.uk/pdbsum/9icz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9icz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A4FFC0_SACEN A4FFC0_SACEN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The pyrroloindole (hexahydropyrrolo[2,3-b]indole, HPI) structural motif is present in a wide range of natural products with various biological activities, yet its chemical synthesis poses a challenge, particularly regarding methylation at the indole C3 position. In nature, S-adenosyl methionine (SAM)-dependent methyltransferases efficiently catalyze this reaction with high stereoselectivity. This study presents the investigation and rational re-design of a potential methyltransferase, termed SeMT, from the actinomycete Saccharopolyspora erythraea. While its three-dimensional structure elucidated via X-ray crystallography confirmed extensive structural similarity to cyclic dipeptide-processing methyltransferases such as SgMT, its putative catalytic center is clearly divergent. Accordingly, wild-type SeMT displayed minimal activity with diketopiperazine (DKP) substrates, triggering an extensive mutagenesis effort aimed at iteratively enhancing this methyltransferase function. This work yielded a variant with appreciable activity, which was comprehensively characterized. Notably, a specific mutation within the catalytic triad of SeMT proved critical not only for its own function but also for the temperature-activity profile of its homolog protein SgMT. Beyond the specific properties of SeMT, these findings hence provide important insights into the active center architecture of indole C3-methyltransferases, supporting further development of these enzymes into refined biocatalysts for synthetic applications.

Re-engineering a transferase scaffold for indole C3 methylation in diketopiperazines.,Haase M, Weiergraber OH, Pietruszka J Protein Sci. 2025 Sep;34(9):e70254. doi: 10.1002/pro.70254. PMID:40878043<ref>PMID:40878043</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9icz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharopolyspora erythraea]]
[[Category: Haase M]]
[[Category: Pietruszka J]]
[[Category: Weiergraeber OH]]