5yng: Difference between revisions
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==Crystal structure of SZ348 in complex with cyclopentene oxide== | |||
<StructureSection load='5yng' size='340' side='right' caption='[[5yng]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5yng]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YNG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YNG FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZS:(1R,5S)-6-OXABICYCLO[3.1.0]HEXANE'>3ZS</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Limonene-1,2-epoxide_hydrolase Limonene-1,2-epoxide hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.8 3.3.2.8] </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=5yng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yng OCA], [http://pdbe.org/5yng PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yng RCSB], [http://www.ebi.ac.uk/pdbsum/5yng PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yng ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/LIMA_RHOER LIMA_RHOER]] Catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol. Can use both the (-) and (+) isomers of limonene-1,2-epoxide as substrates and also has some activity with 1-methylcyclohexene oxide, cyclohexene oxide and indene oxide as substrates. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Directed evolution of limonene epoxide hydrolase (LEH), which catalyzes the hydrolytic desymmetrization reactions of cyclopentene oxide and cyclohexene oxide, results in (R,R)- and (S,S)-selective mutants. Their crystal structures combined with extensive theoretical computations shed light on the mechanistic intricacies of this widely used enzyme. From the computed activation energies of various pathways, we discover the underlying stereochemistry for favorable reactions. Surprisingly, some of the most enantioselective mutants that rapidly convert cyclohexene oxide do not catalyze the analogous transformation of the structurally similar cyclopentene oxide, as shown by additional X-ray structures of the variants harboring this slightly smaller substrate. We explain this puzzling observation on the basis of computational calculations which reveal a disrupted alignment between nucleophilic water and cyclopentene oxide due to the pronounced flexibility of the binding pocket. In contrast, in the stereoselective reactions of cyclohexene oxide, reactive conformations are easily reached. The unique combination of structural and computational data allows insight into mechanistic details of this epoxide hydrolase and provides guidance for future protein engineering in reactions of structurally different substrates. | |||
Structural and Computational Insight into the Catalytic Mechanism of Limonene Epoxide Hydrolase Mutants in Stereoselective Transformations.,Sun Z, Wu L, Bocola M, Chan HCS, Lonsdale R, Kong XD, Yuan S, Zhou J, Reetz MT J Am Chem Soc. 2018 Jan 10;140(1):310-318. doi: 10.1021/jacs.7b10278. Epub 2017, Dec 27. PMID:29232125<ref>PMID:29232125</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5yng" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Limonene-1,2-epoxide hydrolase]] | |||
[[Category: Reetz, M T]] | |||
[[Category: Sun, Z T]] | |||
[[Category: Wu, L]] | [[Category: Wu, L]] | ||
[[Category: | [[Category: Zhou, J H]] | ||
[[Category: | [[Category: Cyclopentene oxide]] | ||
[[Category: | [[Category: Epoxide hydrolase]] | ||
[[Category: Hydrolase]] | |||
Revision as of 08:31, 27 June 2018
Crystal structure of SZ348 in complex with cyclopentene oxideCrystal structure of SZ348 in complex with cyclopentene oxide
Structural highlights
Function[LIMA_RHOER] Catalyzes the conversion of limonene-1,2-epoxide to limonene-1,2-diol. Can use both the (-) and (+) isomers of limonene-1,2-epoxide as substrates and also has some activity with 1-methylcyclohexene oxide, cyclohexene oxide and indene oxide as substrates. Publication Abstract from PubMedDirected evolution of limonene epoxide hydrolase (LEH), which catalyzes the hydrolytic desymmetrization reactions of cyclopentene oxide and cyclohexene oxide, results in (R,R)- and (S,S)-selective mutants. Their crystal structures combined with extensive theoretical computations shed light on the mechanistic intricacies of this widely used enzyme. From the computed activation energies of various pathways, we discover the underlying stereochemistry for favorable reactions. Surprisingly, some of the most enantioselective mutants that rapidly convert cyclohexene oxide do not catalyze the analogous transformation of the structurally similar cyclopentene oxide, as shown by additional X-ray structures of the variants harboring this slightly smaller substrate. We explain this puzzling observation on the basis of computational calculations which reveal a disrupted alignment between nucleophilic water and cyclopentene oxide due to the pronounced flexibility of the binding pocket. In contrast, in the stereoselective reactions of cyclohexene oxide, reactive conformations are easily reached. The unique combination of structural and computational data allows insight into mechanistic details of this epoxide hydrolase and provides guidance for future protein engineering in reactions of structurally different substrates. Structural and Computational Insight into the Catalytic Mechanism of Limonene Epoxide Hydrolase Mutants in Stereoselective Transformations.,Sun Z, Wu L, Bocola M, Chan HCS, Lonsdale R, Kong XD, Yuan S, Zhou J, Reetz MT J Am Chem Soc. 2018 Jan 10;140(1):310-318. doi: 10.1021/jacs.7b10278. Epub 2017, Dec 27. PMID:29232125[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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