Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • 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
Protein Surface Softness Is the Origin of Enzyme Cold-Adaptation of Trypsin
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2014 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 10, no 8, e1003813- p.Article in journal (Refereed) Published
Abstract [en]

Life has effectively colonized most of our planet and extremophilic organisms require specialized enzymes to survive under harsh conditions. Cold-loving organisms (psychrophiles) express heat-labile enzymes that possess a high specific activity and catalytic efficiency at low temperatures. A remarkable universal characteristic of cold-active enzymes is that they show a reduction both in activation enthalpy and entropy, compared to mesophilic orthologs, which makes their reaction rates less sensitive to falling temperature. Despite significant efforts since the early 1970s, the important question of the origin of this effect still largely remains unanswered. Here we use cold-and warm-active trypsins as model systems to investigate the temperature dependence of the reaction rates with extensive molecular dynamics free energy simulations. The calculations quantitatively reproduce the catalytic rates of the two enzymes and further yield high-precision Arrhenius plots, which show the characteristic trends in activation enthalpy and entropy. Detailed structural analysis indicates that the relationship between these parameters and the 3D structure is reflected by significantly different internal protein energy changes during the reaction. The origin of this effect is not localized to the active site, but is found in the outer regions of the protein, where the cold-active enzyme has a higher degree of softness. Several structural mechanisms for softening the protein surface are identified, together with key mutations responsible for this effect. Our simulations further show that single point-mutations can significantly affect the thermodynamic activation parameters, indicating how these can be optimized by evolution.

Place, publisher, year, edition, pages
2014. Vol. 10, no 8, e1003813- p.
National Category
Bioinformatics (Computational Biology)
Identifiers
URN: urn:nbn:se:uu:diva-234207DOI: 10.1371/journal.pcbi.1003813ISI: 000341573600049OAI: oai:DiVA.org:uu-234207DiVA: diva2:757558
Available from: 2014-10-22 Created: 2014-10-15 Last updated: 2017-12-05Bibliographically approved

Open Access in DiVA

fulltext(1735 kB)147 downloads
File information
File name FULLTEXT01.pdfFile size 1735 kBChecksum SHA-512
d9d1d482fb4a529c6f3ea488b6c88c172264645e8dfc2847f5ef9d4d37a6462667268df560868b08407b795952a8da85c9016440603306f2dbec782fd0f81ffb
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Åqvist, Johan
By organisation
Department of Cell and Molecular Biology
In the same journal
PloS Computational Biology
Bioinformatics (Computational Biology)

Search outside of DiVA

GoogleGoogle Scholar
Total: 147 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 644 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • 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