Download MendeleyStructure-based analysis of catalysis and substrate definition in the HIT protein family.
Lima, C.D., Klein, M.G., Hendrickson, W.A.(1997) Science 278: 286-290
- PubMed: 9323207
- DOI: https://doi.org/10.1126/science.278.5336.286
- Primary Citation of Related Structures:
1AV5, 1KPE, 1KPF, 4FIT, 5FIT, 6FIT - 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.
Organizational Affiliation:
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
