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- Title
Structure-based analysis of catalysis and substrate definition in the HIT protein family.
- Authors
Lima, C D; Klein, M G; Hendrickson, W A
- Abstract
The histidine triad (HIT) protein family is among the most ubiquitous and highly conserved in nature, but a biological activity has not yet been identified for any member of the HIT family. Fragile histidine triad protein (FHIT) and protein kinase C interacting protein (PKCI) were used in a structure-based approach to elucidate characteristics of in vivo ligands and reactions. Crystallographic structures of apo, substrate analog, pentacovalent transition-state analog, and product states of both enzymes reveal a catalytic mechanism and define substrate characteristics required for catalysis, thus unifying the HIT family as nucleotidyl hydrolases, transferases, or both. The approach described here may be useful in identifying structure-function relations between protein families identified through genomics.
- Publication
Science (New York, N.Y.), 1997, Vol 278, Issue 5336, p286
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.278.5336.286