Publication Date:
1997-10-10
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lima, C D -- Klein, M G -- Hendrickson, W A -- T32CA09503/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Oct 10;278(5336):286-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9323207" target="_blank"〉PubMed〈/a〉
Keywords:
*Acid Anhydride Hydrolases
;
Adenosine/metabolism
;
Adenosine Diphosphate/analogs & derivatives/metabolism
;
Adenosine Monophosphate/metabolism
;
Adenosine Triphosphate/metabolism
;
Binding Sites
;
Catalysis
;
Crystallography, X-Ray
;
Dimerization
;
Dinucleoside Phosphates/metabolism
;
Hydrogen Bonding
;
*Neoplasm Proteins
;
Nerve Tissue Proteins/chemistry/*metabolism
;
Protein Structure, Secondary
;
Proteins/chemistry/*metabolism
;
Structure-Activity Relationship
;
Substrate Specificity
;
Tungsten Compounds/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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