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Titolo:
A model of the pressure dependence of the enantio selectivity of Candida rugosa lipase towards (+/-)-menthol
Autore:
Kahlow, UHM; Schmid, RD; Pleiss, J;
Indirizzi:
Univ Stuttgart, Inst Tech Biochem, D-70569 Stuttgart, Germany Univ Stuttgart Stuttgart Germany D-70569 hem, D-70569 Stuttgart, Germany
Titolo Testata:
PROTEIN SCIENCE
fascicolo: 10, volume: 10, anno: 2001,
pagine: 1942 - 1952
SICI:
0961-8368(200110)10:10<1942:AMOTPD>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
PSEUDOMONAS-CEPACIA LIPASE; CATALYZED TRANSESTERIFICATION REACTIONS; MOLECULAR-DYNAMICS SIMULATION; SECONDARY ALCOHOLS; 2-ARYLPROPIONIC ESTERS; QUANTITATIVE-ANALYSES; KINETIC RESOLUTION; RHIZOMUCOR-MIEHEI; MICROBIAL LIPASES; 3-HYDROXY ESTERS;
Keywords:
molecular dynamics; elevated pressure; stereoselectivity; Candida rugosa lipase; enantioselectivity; essential water;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: Pleiss, J Univ Stuttgart, Inst Tech Biochem, Allmandring 31, D-70561 Stuttgart, Germany Univ Stuttgart Allmandring 31 Stuttgart Germany D-70561 Germany
Citazione:
U.H.M. Kahlow et al., "A model of the pressure dependence of the enantio selectivity of Candida rugosa lipase towards (+/-)-menthol", PROTEIN SCI, 10(10), 2001, pp. 1942-1952

Abstract

Transesterification of (+/-)-menthol using propionic acid anhydride and Candida rugosa lipase was performed in chloroform and water at different pressures (1, 10, 50, and 100 bar) to study the pressure dependence of enantioselectivity E. As a result, E significantly decreased with increasing pressure from E = 55 (1 bar) to E = 47 (10 bar), E = 37 (50 bar), and E = 9 (100 bar). To rationalize the experimental findings, molecular dynamics simulations of Candida rugosa lipase were carried out. Analyzing the lipase geometry at 1, 10, 50, and 100 bar revealed a cavity in the Candida rugosa lipase. The cavity leads from a position on the surface distinct from the substrate binding site to the core towards the active site, and is limited by F415 and the catalytic H449. In the crystal structure of the Candida rugosa lipase, this cavity is filled with six water molecules. The number of water molecules in this cavity gradually increased with increasing pressure: six molecules in the simulation at 1 bar, 10 molecules at 10 bar, 12 molecules at 50 bar, and 13 molecules at 100 bar. Likewise, the volume of the cavity progressively increased from about 1864 Angstrom (3) in the simulation at 1 bar to 2529 Angstrom (3) at 10 bar, 2526 Angstrom (3) at 50 bar, and 2617 Angstrom (3) at 100 bar. At 100 bar, one water molecule slipped between F415 and H449, displacing the catalytic histidine side chain and thus opening thecavity to form a continuous water channel. The rotation of the side chain leads to a decreased distance between the H449-N epsilon and the (+)-menthyl-oxygen (nonpreferred enantiomer) in the acyl enzyme intermediate, a factor determining the enantioselectivity of the lipase. Although the geometry of the preferred enantiomer is similar in all simulations, the geometry of the nonpreferred enantiomer gets gradually more reactive. This observation correlates with the gradually decreasing enantioselectivity E.

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Documento generato il 22/10/20 alle ore 03:42:16