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
Molecular dynamics simulations of a branched tetradecasaccharide substrate in the active site of a xyloglucan endo-transglycosylase
KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
KTH, School of Biotechnology (BIO), Glycoscience.
Show others and affiliations
(English)In: Molecular Simulation, ISSN 0892-7022, E-ISSN 1029-0435Article in journal (Refereed) In press
Abstract [en]

Molecular dynamics (MD) simulations of the tetradecasaccharide XXXGXXXG in complex with the hybrid aspen xyloglucan endo-transglycosylase PttXET16-34 have been performed and analyzed with respect to structure, dynamics, flexibility and ligand interactions. Notably, the charge state of the so-called “helper residue” Asp87, which lies between the catalytic nucleophile (Glu85) and general acid/base (Glu89) residues on the same beta strand, had a significant effect on PttXET16-34 active site structure. When Asp87 was deprotonated, electrostatic repulsion forced the nucleophile Glu85 away from C-1 of the sugar ring in subsite -1 and the electrophile Glu89 was also weakened due to the formation of a hydrogen bond to Asp87, whereas the protonation of Asp87 resulted in the formation of a hydrogen bond with the catalytic nucleophile and correct positioning of the catalytic machinery. The results suggest that catalysis in glycoside hydrolase family 16, and by extension clan GH-B enzymes, is optimal when the catalytic nucleophile is deprotonated for nucleophilic attack on the substrate, while the “helper residue” and general acid/base residue are both in their conjugate-acid forms to align the nucleophile and deliver a proton to the departing sugar, respectively.

Place, publisher, year, edition, pages
Taylor and Francis.
Keyword [en]
Xyloglucan, Xyloglucan binding protein, Complex, Molecular Dynamics simulation, Glycam force field
Identifiers
URN: urn:nbn:se:kth:diva-33574OAI: oai:DiVA.org:kth-33574DiVA: diva2:416143
Note
QS 2011Available from: 2011-05-10 Created: 2011-05-10 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Molecular Dynamics Simulations of Biomimetic Carbohydrate Materials
Open this publication in new window or tab >>Molecular Dynamics Simulations of Biomimetic Carbohydrate Materials
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The present thesis honors contemporary molecular dynamics simulation methodologies which provide powerful means to predict data, interpret observations and widen our understanding of the dynamics, structures and interactions of carbohydrate systems. With this as starting point my thesis work embarked on several cutting edge problems summarized as follows.

In my first work the thermal response in crystal cellulose Iβ was studied with special emphasis on the temperature dependence of the crystal unit cell parameters and the organization of the hydrogen bonding network. The favorable comparison with available experimental data, like the phase transition temperature, the X-ray diffraction crystal structures of cellulose Iβ at room and high temperatures, and temperature dependent IR spectra supported our conclusions on the good performance of the GLYCAM06 force field for the description of cellulose crystals, and that a cautious parameterization of the non-bonded interaction terms in a force field is critical for the correct prediction of the thermal response in cellulose crystals.

The adsorption properties of xyloglucans on the cellulose Iβ surface were investigated in my second paper. In our simulations, the interaction energies between xyloglucan and cellulose in water were found to be considerably lower than those in vacuo. The van der Waals interactions played a prevailing role over the electrostatic interactions in the adsorption. Though the variation in one side chain did not have much influence on the interaction energy and the binding affinity, it did affect the structural properties of the adsorbed xyloglucans.

The interaction of the tetradecasaccharide XXXGXXXG in complex with the hybrid aspen xyloglucan endo-transglycosylase PttXET16-34 was studied in the third paper. The effect of the charge state of the “nucleophile helper” residue Asp87 on the PttXET16-34 active site structure was emphasized. The results indicate that the catalysis is optimal when the catalytic nucleophile is deprotonated, while the “helper” residue and general acid/base residue are both protonated.

In my forth paper, the working mechanism for a redox-responsive bistable [2]rotaxane based on an α-cyclodextrin ring was investigated. The umbrella sampling technique was employed to calculate the free energy profiles for the shuttling motion of the α-cyclodextrin ring between two recognition sites on the dumbbell of the rotaxane. The calculated free energy profiles verified the binding preferences observed experimentally. The driving force for the shuttling movement of the α-cyclodextrin ring was revealed by the analysis of the free energy components.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2011. viii, 66 p.
Series
Trita-BIO-Report, ISSN 1654-2312 ; 2011:12
Keyword
molecular dynamics simulation, carbohydrate, cellulose, xyloglucan, cyclodextrin
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-33439 (URN)978-91-7415-966-0 (ISBN)
Public defence
2011-05-31, FB42, AlbaNova, Roslagstullsbacken 21, Stockholm, 14:00 (English)
Opponent
Supervisors
Funder
Swedish e‐Science Research Center
Note
QC 20110513Available from: 2011-05-13 Created: 2011-05-06 Last updated: 2012-05-24Bibliographically approved

Open Access in DiVA

No full text

Authority records BETA

Ågren, Hans

Search in DiVA

By author/editor
Mark, PekkaZhang, QiongBrumer, HarryÅgren, Hans
By organisation
Theoretical Chemistry and BiologyGlycoscience
In the same journal
Molecular Simulation

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 60 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