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Thermomyces lanuginosus Lipase with Closed Lid Catalyzes Elimination of Acetic Acid from 11‐Acetyl‐Prostaglandin E 2
Author(s) -
Villo Ly,
Metsala Andrus,
Tamp Sven,
Parve Jaan,
Vallikivi Imre,
Järving Ivar,
Samel Nigulas,
Lille Ülo,
Pehk Tõnis,
Parve Omar
Publication year - 2014
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201400019
Subject(s) - chemistry , lipase , methanol , catalysis , solvation , benzene , acetic acid , organic chemistry , docking (animal) , combinatorial chemistry , stereochemistry , enzyme , solvent , medicine , nursing
A lipase may catalyze either one or more of the three reactions of 11‐acetyl‐prostaglandin E 2 in methanol‐containing reaction medium: esterification, deacetylation, and/or elimination. The catalytic performance depends on the lipase and on the methanol content. An increase in the methanol concentration in benzene from 5 % to 95 % leads to the exclusive switch of reactions from esterification to elimination catalyzed by Thermomyces lanuginosus lipase (TLL). To explain the switch, molecular dynamics simulations of solvation of TLL in benzene and in methanol were performed. Solvation in methanol leads to the closing of the lid. The repositioning of the oxyanion hole towards the catalytic triad blocks the catalysis of ester synthesis whereas enabling TLL to act as an acetyl‐β‐ketol eliminase. In benzene the lid is open, allowing esterification to occur. Docking analysis of 11‐acetyl‐prostaglandin E 2 into the active site of the solvated TLL structures suggested the occurrence of reactions in accordance with the experiment.