Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Quantum Chemical Modeling of Enzymatic Reactions: The Case of Histone Lysine Methyltransferase
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University.
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University.
2010 (Engelska)Ingår i: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 31, nr 8, s. 1707-1714Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Quantum chemical cluster models of enzyme active sites are today an important and powerful tool in the study of various aspects of enzymatic reactivity. This methodology has been applied to a wide spectrum of reactions and many important mechanistic problems have been solved. Herein, we report a systematic study of the reaction mechanism of the histone lysine methyltransferase (HKMT) SET7/9 enzyme, which catalyzes the methylation of the N-terminal histone tail of the chromatin structure. In this study, HKMT SET7/9 serves as a representative case to examine the modeling approach for the important class of methyl transfer enzymes. Active site models of different sizes are used to evaluate the methodology. In particular, the dependence of the calculated energies on the model size, the influence of the dielectric medium, and the particular choice of the dielectric constant are discussed. In addition, we examine the validity of some technical aspects, such as geometry optimization in solvent or with a large basis set, and the use of different density functional methods.

Ort, förlag, år, upplaga, sidor
2010. Vol. 31, nr 8, s. 1707-1714
Nyckelord [en]
enzyme catalysis, density functional theory, methyltransferase
Nationell ämneskategori
Teoretisk kemi
Identifikatorer
URN: urn:nbn:se:kth:diva-24819DOI: 10.1002/jcc.21458ISI: 000277483500016OAI: oai:DiVA.org:kth-24819DiVA, id: diva2:353458
Anmärkning
QC 20100927. Uppdaterad från manuskript till artikel (20100927).Tillgänglig från: 2010-09-27 Skapad: 2010-09-27 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
Ingår i avhandling
1. Quantum Chemical Modeling of Enzymatic Methyl Transfer Reactions
Öppna denna publikation i ny flik eller fönster >>Quantum Chemical Modeling of Enzymatic Methyl Transfer Reactions
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

In this thesis, quantum chemistry, in particular the B3LYP density functional method, is used to investigate a number of methyl transfer enzymes. Quantum chemical methodology is today a very important tool in the elucidation of properties and reaction mechanisms of enzyme active sites. The enzymes considered in this thesis are the S-adenosyl L-methionine-dependent enzymes - glycine N-methyltransferase, guanidinoacetate methyltransferase, phenylethanolamine N-methyltransferase, and histone lysine methyltransferase. In addition, the reaction mechanism of the DNA repairing enzyme O6-methylguanine methyltransferase is studied. Active site models of varying sizes were designed and stationary points along the reaction paths were optimized and characterized. Potential energy surfaces for the reactions were calculated and the feasibility of the suggested reaction mechanisms was able to be judged. By systematically increasing the size of the models, deeper insight into the details of the reactions was obtained, the roles of the various active site residues could be analyzed, and, very importantly, the adopted modeling strategy was evaluated.

Ort, förlag, år, upplaga, sidor
Stockholm: KTH, 2008. s. ix, 51
Serie
Trita-BIO-Report, ISSN 1654-2312 ; 2008:26
Nyckelord
reaction mechanism
Nationell ämneskategori
Teoretisk kemi
Identifikatorer
urn:nbn:se:kth:diva-9695 (URN)978-91-7415-171-8 (ISBN)
Disputation
2008-12-18, FB53, AlbaNova, Roslagstullsbacken 21, Stockholm, 10:00 (Engelska)
Opponent
Handledare
Anmärkning
QC 20100927Tillgänglig från: 2008-12-04 Skapad: 2008-11-27 Senast uppdaterad: 2010-09-27Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltext

Sök vidare i DiVA

Av författaren/redaktören
Georgieva, PolinaHimo, Fahmi
I samma tidskrift
Journal of Computational Chemistry
Teoretisk kemi

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 111 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf