In:
European Journal of Inorganic Chemistry, Wiley, Vol. 2009, No. 20 ( 2009-07), p. 2967-2972
Abstract:
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 nucleophilic 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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Type of Medium:
Online Resource
ISSN:
1434-1948
,
1099-0682
DOI:
10.1002/ejic.v2009:20
DOI:
10.1002/ejic.200900202
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
1475009-0
Permalink