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Switched enantiopreference of Humicola lipase for 2-phenoxyalkanoic acid ester homologs can be rationalized by different substrate binding modes
KTH, Superseded Departments, Biotechnology.ORCID iD: 0000-0002-9577-832X
KTH, Superseded Departments, Biotechnology.
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1999 (English)In: Tetrahedron: asymmetry, ISSN 0957-4166, E-ISSN 1362-511X, Vol. 10, no 21, 4191-4202 p.Article in journal (Refereed) Published
Abstract [en]

Humicola lanuginosa lipase was used for enantioselective hydrolyses of a series of homologous 2-phenoxyalkanoic acid ethyl esters. The enantioselectivity (E-value) of the enzyme changed from an (R)-enantiomer preference for the smallest substrate, 2-phenoxypropanoic acid ester, to an (S)-enantiomer preference for the homologous esters with longer acyl moieties. The E-values span the range from E=13 (R) to E=56 (S). A molecular modeling study identified two different substrate-binding modes for each enantiomer. We found that the enantiomers favored different modes. This discovery provided a model that offered a rational explanation for the observed switch in enantioselectivity. (C) 1999 Elsevier Science Ltd. All rights reserved.

Place, publisher, year, edition, pages
1999. Vol. 10, no 21, 4191-4202 p.
Keyword [en]
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:kth:diva-25181ISI: 000083948700019OAI: diva2:356311
QC 20101012 NR 20140804Available from: 2010-10-12 Created: 2010-10-12 Last updated: 2012-02-03Bibliographically approved
In thesis
1. Molecular modelling - understanding and prediction of enzyme selectivity.
Open this publication in new window or tab >>Molecular modelling - understanding and prediction of enzyme selectivity.
2009 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Molecular modelling strategies for evaluation of enzyme selectivity wereinvestigated with a focus on principles of how molecular interactionscould be evaluated to provide information about selectivity. Althoughmolecular modelling provides tools for evaluation of geometrical andenergy features of molecular systems, no general strategies for evaluationof enzyme selectivity exist. Geometrical analyses can be based uponinspection and reasoning about molecular interactions, which provide aneasily accessible way to gain information, but suffer from the risk of biasput in by the modeller. They can also be based on geometrical features ofmolecular interactions such as bond lengths and hydrogen-bond formation.Energy analyses are appealing for their modeller independenceand for the possibility to predict not only stereopreference, but also itsmagnitude.In this thesis, four examples of enantio- or regioselective serinehydrolase-catalysed reaction systems are presented together with developedmodelling protocols for explanation, prediction or enhancement ofselectivity. Geometrical as well as energy-based methodology were used,and provided an understanding of the structural basis of enzymeselectivity. In total, the protocols were successful in making qualitative explanationsand predictions of stereoselectivity, although quantitative determinationswere not achieved.

Place, publisher, year, edition, pages
Stockholm: KTH, 2009. 27 p.
Trita-BIO-Report, ISSN 1654-2312 ; 2009:11
molecular modelling; regioselectivity; enantioselectivity; molecular dynamics; serine hydrolase; stereospecificity
National Category
Biochemistry and Molecular Biology
urn:nbn:se:kth:diva-10532 (URN)978-91-7415-325-5 (ISBN)
Available from: 2009-05-26 Created: 2009-05-25 Last updated: 2010-10-12Bibliographically approved

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Berglund, PerFransson, LindaHolmquist, MatsMartinelle, MatsHult, Karl
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