Electrostatic Guidance of Glycosyl Cation Migration along the Reaction Coordinate of Uracil DNA Glycosylase

Mario A. Bianchet, Lauren A. Seiple, Yu Lin Jiang, Yoshitaka Ichikawa, L. Mario Amzel, James T. Stivers

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

The DNA repair enzyme uracil DNA glycosylase has been crystallized with a cationic 1-aza-2′-deoxyribose-containing DNA that mimics the ultimate transition state of the reaction in which the water nucleophile attacks the anomeric center of the oxacarbenium ion-uracil anion reaction intermediate. Comparison with substrate and product structures, and the previous structure of the intermediate determined by kinetic isotope effects, reveals an exquisite example of geometric strain, least atomic motion, and electrophile migration in biological catalysis. This structure provides a rare opportunity to reconstruct the detailed structural transformations that occur along an enzymatic reaction coordinate.

Original languageEnglish (US)
Pages (from-to)12455-12460
Number of pages6
JournalBiochemistry
Volume42
Issue number43
DOIs
StatePublished - Nov 4 2003

ASJC Scopus subject areas

  • Biochemistry

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