Electrostatic guidance of glycosyl cation migration along the reaction coordinate of uracil DNA glycosylase.

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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Bianchet MA,Seiple LA,Jiang YL,Ichikawa Y,Amzel LM,Stivers JT

doi

10.1021/bi035372+

subject

Has Abstract

pub_date

2003-11-04 00:00:00

pages

12455-60

issue

43

eissn

0006-2960

issn

1520-4995

journal_volume

42

pub_type

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