6q7n: Difference between revisions
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<StructureSection load='6q7n' size='340' side='right'caption='[[6q7n]], [[Resolution|resolution]] 2.02Å' scene=''> | <StructureSection load='6q7n' size='340' side='right'caption='[[6q7n]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6q7n]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6q7n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q7N FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AC0:1-PHENYLETHANONE'>AC0</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6q7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q7n OCA], [https://pdbe.org/6q7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q7n RCSB], [https://www.ebi.ac.uk/pdbsum/6q7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q7n ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/O58216_PYRHO O58216_PYRHO] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Pyrococcus horikoshii]] | ||
[[Category: | [[Category: Levy CW]] | ||
Latest revision as of 14:54, 24 January 2024
Crystal structure of BH32 alkylated with the mechanistic inhibitor 2-bromoacetophenoneCrystal structure of BH32 alkylated with the mechanistic inhibitor 2-bromoacetophenone
Structural highlights
FunctionPublication Abstract from PubMedThe combination of computational design and laboratory evolution is a powerful and potentially versatile strategy for the development of enzymes with new functions(1-4). However, the limited functionality presented by the genetic code restricts the range of catalytic mechanisms that are accessible in designed active sites. Inspired by mechanistic strategies from small-molecule organocatalysis(5), here we report the generation of a hydrolytic enzyme that uses Ndelta-methylhistidine as a non-canonical catalytic nucleophile. Histidine methylation is essential for catalytic function because it prevents the formation of unreactive acyl-enzyme intermediates, which has been a long-standing challenge when using canonical nucleophiles in enzyme design(6-10). Enzyme performance was optimized using directed evolution protocols adapted to an expanded genetic code, affording a biocatalyst capable of accelerating ester hydrolysis with greater than 9,000-fold increased efficiency over free Ndelta-methylhistidine in solution. Crystallographic snapshots along the evolutionary trajectory highlight the catalytic devices that are responsible for this increase in efficiency. Ndelta-methylhistidine can be considered to be a genetically encodable surrogate of the widely employed nucleophilic catalyst dimethylaminopyridine(11), and its use will create opportunities to design and engineer enzymes for a wealth of valuable chemical transformations. Design and evolution of an enzyme with a non-canonical organocatalytic mechanism.,Burke AJ, Lovelock SL, Frese A, Crawshaw R, Ortmayer M, Dunstan M, Levy C, Green AP Nature. 2019 May 27. pii: 10.1038/s41586-019-1262-8. doi:, 10.1038/s41586-019-1262-8. PMID:31132786[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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