Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-7-5
pubmed:abstractText
The cytidine deaminase substrate analog inhibitor 3-deazacytidine binds with its 4-amino group inserted into a site previously identified as a probable binding site for the leaving ammonia group. Binding to this site shifts the pyrimidine ring significantly further from the activated water molecule than the position it occupies in either of two complexes with compounds capable of hydrogen bonding at the 3-position of the ring [Xiang et al. (1995) Biochemistry 34, 4516-4523]. Difference Fourier maps between the deazacytidine, dihydrozebularine, and zebularine--hydrate inhibitor complexes suggest that the ring itself moves successively toward the activated water, leaving the amino group behind in this site as the substrate complex approaches the transition state. They also reveal systematic changes in a single zinc-sulfur bond distance. These correlate with chemical changes expected as the substrate approaches the tetrahedral transition state, in which the zinc-activated hydroxyl group develops maximal negative charge and forms a short hydrogen bond to the neighboring carboxylate group of Glu 104. Empirical bond valence relationships suggest that the Zn-S gamma 132 bond functions throughout the reaction as a "valence buffer" that accommodates changing negative charge on the hydroxyl group. Similar structural features in alcohol dehydrogenase suggest that analogous mechanisms may be a general feature of catalysis by zinc enzymes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1335-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Cytidine deaminase complexed to 3-deazacytidine: a "valence buffer" in zinc enzyme catalysis.
pubmed:affiliation
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599-7260, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't