Structural basis for catalytically restrictive dynamics of a high-energy enzyme stateShow others and affiliations
2015 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 6, article id 7644Article in journal (Refereed) Published
Abstract [en]
An emerging paradigm in enzymology is that transient high-energy structural states play crucial roles in enzymatic reaction cycles. Generally, these high-energy or ‘invisible’ states cannot be studied directly at atomic resolution using existing structural and spectroscopic techniques owing to their low populations or short residence times. Here we report the direct NMR-based detection of the molecular topology and conformational dynamics of a catalytically indispensable high-energy state of an adenylate kinase variant. On the basis of matching energy barriers for conformational dynamics and catalytic turnover, it was found that the enzyme’s catalytic activity is governed by its dynamic interconversion between the high-energy state and a ground state structure that was determined by X-ray crystallography. Our results show that it is possible to rationally tune enzymes’ conformational dynamics and hence their catalytic power—a key aspect in rational design of enzymes catalysing novel reactions.
Place, publisher, year, edition, pages
Macmillan Publishers Ltd., 2015. Vol. 6, article id 7644
Keywords [en]
Biological sciences, Biophysics, Biochemistry
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:umu:diva-106747DOI: 10.1038/ncomms8644ISI: 000358857800018Scopus ID: 2-s2.0-84936764226OAI: oai:DiVA.org:umu-106747DiVA, id: diva2:844540
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation2015-08-062015-08-062023-03-28Bibliographically approved