6q7n: Difference between revisions

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-'''Unreleased structure'''
-The entry 6q7n is ON HOLD
+==Crystal structure of BH32 alkylated with the mechanistic inhibitor 2-bromoacetophenone==
+<StructureSection load='6q7n' size='340' side='right'caption='[[6q7n]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6q7n]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q7N FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6q7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q7n OCA], [http://pdbe.org/6q7n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q7n RCSB], [http://www.ebi.ac.uk/pdbsum/6q7n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q7n ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 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.
-Authors: Levy, C.W.
+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<ref>PMID:31132786</ref>
-Description: Crystal structure of BH32 alkylated with the mechanistic inhibitor 2-bromoacetophenone
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Levy, C.W]]
+<div class="pdbe-citations 6q7n" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Levy, C W]]
+[[Category: Computationally designed enzyme]]
+[[Category: Hydrolase]]