Active species for the ground-state complex of cytidine deaminase: A linear-scaling quantum mechanical investigation


Journal Article

We present results of large-scale (1330 atoms) linear-scaling quantum mechanical semiempirical (PM3) simulations done to optimize geometries surrounding the active site within the enzyme cytidine deaminase. We make a strong prediction about the structure of the active site for the active species, based on the energetics of the calculated structures and comparisons to X-ray crystallographic data. The lowest energy structure indicates that Zn-OH- is the active species formed prior to nucleophilic attack of the ligand, that the active species of Glu-104 is with Oε2 protonated and hydrogen-bonded with N3 of the ligand, and that the C4 and OH- atoms are significantly closer than is permitted by their van der Waals radii. In addition, we predict structures corresponding to the low-pH and high-pH states in the active site of the enzyme.

Full Text

Duke Authors

Cited Authors

  • Lewis, JP; Carter, CW; Hermans, J; Pan, W; Lee, TS; Yang, W

Published Date

  • June 10, 1998

Published In

Volume / Issue

  • 120 / 22

Start / End Page

  • 5407 - 5410

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja973522w

Citation Source

  • Scopus