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Science. 1997 Oct 10;278(5336):286-90.

Structure-based analysis of catalysis and substrate definition in the HIT protein family.

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  • 1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.

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.

PMID:
9323207
[PubMed - indexed for MEDLINE]
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