Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The modelling and kinetic investigation of the lipase-catalysed acetylation of stereoisomeric prostaglandins
KTH, School of Biotechnology (BIO), Biochemistry.
KTH, School of Biotechnology (BIO), Biochemistry.
Show others and affiliations
2005 (English)In: Journal of Molecular Catalysis B: Enzymatic, ISSN 1381-1177, E-ISSN 1873-3158, Vol. 35, no 1-3, 62-69 p.Article in journal (Refereed) Published
Abstract [en]

The lipase-catalysed acetylation of the hydroxyl groups of five stereoisomeric prostaglandins of type F was investigated by means of molecular dynamics simulations and the results compared with experimental observations. An NMR spectroscopic monitoring was performed to estimate reaction velocities and the regioselectivity. A molecular modelling protocol that could qualitatively differentiate between the OH groups of prostaglandins being either accessible or unaccessible to the Candida antarctica lipase B (CALB) catalysed acetylation was developed. The protocol developed analysed the protein structure deformation, the content of essential hydrogen bonds and the function-based subset energy of tetrahedral intermediates along the molecular dynamics simulations trajectory. The tetrahedral intermediates displaying a deformation RMS value lower than 3.0 angstrom, an essential hydrogen bond content over 50% and a subset energy less than -95 kJ/mol were classified active. In total, the accessibility of 16 out of 17 different prostaglandin OH groups was correctly predicted.

Place, publisher, year, edition, pages
2005. Vol. 35, no 1-3, 62-69 p.
Keyword [en]
lipase-catalysed acetylation, Novozym 435, low-water media, monitoring by H-1 NMR, prostaglandin, molecular dynamics simulations, enantiomerically pure diastereomers, candida-antarctica, nucleic-acids, force-field, isoprostanes, physiology, proteins, ester
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-14929DOI: 10.1016/j.molcatb.2005.05.008ISI: 000230671100011Scopus ID: 2-s2.0-21644442447OAI: oai:DiVA.org:kth-14929DiVA: diva2:332970
Note
QC 20100525Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically 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.
Series
Trita-BIO-Report, ISSN 1654-2312 ; 2009:11
Keyword
molecular modelling; regioselectivity; enantioselectivity; molecular dynamics; serine hydrolase; stereospecificity
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-10532 (URN)978-91-7415-325-5 (ISBN)
Presentation
(English)
Supervisors
Available from: 2009-05-26 Created: 2009-05-25 Last updated: 2010-10-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textScopus

Search in DiVA

By author/editor
Fransson, LindaHult, Karl
By organisation
Biochemistry
In the same journal
Journal of Molecular Catalysis B: Enzymatic
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 41 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf