Abstract
An analysis of the high resolution 3D structures of zinc enzymes shows that the Zn−His−carboxyl(ate)−HX (X = OH or NH) H-bond motif is common. We investigate here the influence of this motif in the active site of horse liver alcohol dehydrogenase, which features the Zn−His−Asp−H2O motif. Density functional theory calculations are carried out on models of the active site complexed with the NAD+ cofactor, in which the metal ion binds either the alcohol substrate [Bahnson et al. Proc. Natl. Acad. Sci. U. S.A 1997, 94, 12797−12802]1 or a water molecule [Meijers et al. J. Biol. Chem. 2001, 276, 9316−9321].2 Our calculations suggest that in both complexes the presence of Asp49 significantly affects the structural and electronic properties of the metal site. Furthermore, they show that inclusion of the Asp bound water molecule is required to describe the energetics correctly. Finally, they suggest that the Asp49/water pattern could play a role in the enzymatic reaction.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.