6fnt: Difference between revisions
m Protected "6fnt" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
The | ==Ergothioneine-biosynthetic methyltransferase EgtD in complex with pyrrolidinohistidine== | ||
<StructureSection load='6fnt' size='340' side='right' caption='[[6fnt]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6fnt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FNT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FNT FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AVO:Pyrrolidinohistidine'>AVO</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-histidine_N(alpha)-methyltransferase L-histidine N(alpha)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.44 2.1.1.44] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fnt OCA], [http://pdbe.org/6fnt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fnt RCSB], [http://www.ebi.ac.uk/pdbsum/6fnt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fnt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/A0A0D6J225_MYCSM A0A0D6J225_MYCSM]] Catalyzes the SAM-dependent triple methylation of the alpha-amino group of histidine to form hercynine, a step in the biosynthesis pathway of ergothioneine.[HAMAP-Rule:MF_02037] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ergothioneine is an emerging factor in cellular redox homeostasis in bacteria, fungi, plants, and animals. Reports that ergothioneine biosynthesis may be important for the pathogenicity of bacteria and fungi raise the question as to how this pathway is regulated and whether the corresponding enzymes may be therapeutic targets. The first step in ergothioneine biosynthesis is catalyzed by the methyltransferase EgtD that converts histidine into N-alpha-trimethylhistidine. This report examines the kinetic, thermodynamic and structural basis for substrate, product, and inhibitor binding by EgtD from Mycobacterium smegmatis. This study reveals an unprecedented substrate binding mechanism and a fine-tuned affinity landscape as determinants for product specificity and product inhibition. Both properties are evolved features that optimize the function of EgtD in the context of cellular ergothioneine production. On the basis of these findings, we developed a series of simple histidine derivatives that inhibit methyltransferase activity at low micromolar concentrations. Crystal structures of inhibited complexes validate this structure- and mechanism-based design strategy. | |||
Inhibition and Regulation of the Ergothioneine Biosynthetic Methyltransferase EgtD.,Misson L, Burn R, Vit A, Hildesheim J, Beliaeva MA, Blankenfeldt W, Seebeck FP ACS Chem Biol. 2018 May 18;13(5):1333-1342. doi: 10.1021/acschembio.8b00127. Epub, 2018 Apr 16. PMID:29658702<ref>PMID:29658702</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6fnt" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Blankenfeldt, W]] | [[Category: Blankenfeldt, W]] | ||
[[Category: Seebeck, F P]] | |||
[[Category: Vit, A]] | [[Category: Vit, A]] | ||
[[Category: Ergothioneine]] | |||
[[Category: Inhibitor complex]] | |||
[[Category: Methyltransferase]] | |||
[[Category: Transferase]] | |||
Latest revision as of 10:42, 14 June 2018
Ergothioneine-biosynthetic methyltransferase EgtD in complex with pyrrolidinohistidineErgothioneine-biosynthetic methyltransferase EgtD in complex with pyrrolidinohistidine
Structural highlights
Function[A0A0D6J225_MYCSM] Catalyzes the SAM-dependent triple methylation of the alpha-amino group of histidine to form hercynine, a step in the biosynthesis pathway of ergothioneine.[HAMAP-Rule:MF_02037] Publication Abstract from PubMedErgothioneine is an emerging factor in cellular redox homeostasis in bacteria, fungi, plants, and animals. Reports that ergothioneine biosynthesis may be important for the pathogenicity of bacteria and fungi raise the question as to how this pathway is regulated and whether the corresponding enzymes may be therapeutic targets. The first step in ergothioneine biosynthesis is catalyzed by the methyltransferase EgtD that converts histidine into N-alpha-trimethylhistidine. This report examines the kinetic, thermodynamic and structural basis for substrate, product, and inhibitor binding by EgtD from Mycobacterium smegmatis. This study reveals an unprecedented substrate binding mechanism and a fine-tuned affinity landscape as determinants for product specificity and product inhibition. Both properties are evolved features that optimize the function of EgtD in the context of cellular ergothioneine production. On the basis of these findings, we developed a series of simple histidine derivatives that inhibit methyltransferase activity at low micromolar concentrations. Crystal structures of inhibited complexes validate this structure- and mechanism-based design strategy. Inhibition and Regulation of the Ergothioneine Biosynthetic Methyltransferase EgtD.,Misson L, Burn R, Vit A, Hildesheim J, Beliaeva MA, Blankenfeldt W, Seebeck FP ACS Chem Biol. 2018 May 18;13(5):1333-1342. doi: 10.1021/acschembio.8b00127. Epub, 2018 Apr 16. PMID:29658702[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||