Theoretical study of the RNA hydrolysis mechanism of the dinuclear zinc enzyme RNase Z
2009 (English)In: European Journal of Inorganic Chemistry, ISSN 1434-1948, E-ISSN 1099-0682, Vol. 2009, no 20, 2967-2972 p.Article in journal (Refereed) Published
RNase Z is a dinuclear zinc enzyme that catalyzes the removal of the tRNA 3'-end trailer. Density functional theory is used to investigate the phosphodiester hydrolysis mechanism of this enzyme with a model of the active site constructed on the basis of the crystal structure. The calculations imply that the reaction proceeds through two steps. The first step is a nucleophihc attack by a bridging hydroxide coupled with protonation of the leaving group by a Glu-His diad. Subsequently, a water molecule activated by the same Glu-His diad makes a reverse attack, regenerating the bridging hydroxide. The second step is calculated to be the rate-limiting step with a barrier of 18 kcal/mol, in good agreement with experimental kinetic studies. Both zinc ions participate in substrate binding and orientation, facilitating nucleophilic attack. In addition, they act as electrophilic catalysts to stabilize the pentacoordinate trigonal-bipyramidal transition states.
Place, publisher, year, edition, pages
Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA , 2009. Vol. 2009, no 20, 2967-2972 p.
Enzyme catalysis; Metalloenzymes; Dinuclear zinc enzymes; Density functional calculations; Hydrolysis; Reaction mechanisms; Zinc
Other Basic Medicine
IdentifiersURN: urn:nbn:se:su:diva-31365DOI: 10.1002/ejic.200900202ISI: 000268290000010OAI: oai:DiVA.org:su-31365DiVA: diva2:276197