Structure-based analysis of catalysis and substrate definition in the HIT protein family.
Article Details
- CitationCopy to clipboard
Lima CD, Klein MG, Hendrickson WA
Structure-based analysis of catalysis and substrate definition in the HIT protein family.
Science. 1997 Oct 10;278(5336):286-90.
- PubMed ID
- 9323207 [ View in PubMed]
- 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.