TY - JOUR
T1 - Sequence and structure classification of kinases
AU - Cheek, Sara
AU - Zhang, Hong
AU - Grishin, Nick V.
N1 - Funding Information:
This work was supported, in part, by National Institutes of Health grant GM63689 (to H.Z.) and the Welch Foundation grant I-1505 (to N.V.G.).
PY - 2002
Y1 - 2002
N2 - Kinases are a ubiquitous group of enzymes that catalyze the phosphoryl transfer reaction from a phosphate donor (usually ATP) to a receptor substrate. Although all kinases catalyze essentially the same phosphoryl transfer reaction, they display remarkable diversity in their substrate specificity, structure, and the pathways in which they participate. In order to learn the relationship between structural fold and functional specificities in kinases, we have done a comprehensive survey of all available kinase sequences (>17,000) and classified them into 30 distinct families based on sequence similarities. Of these families, 19, covering nearly 98% of all sequences, fall into seven general structural folds for which three-dimensional structures are known. These fold groups include some of the most widespread protein folds, such as Rossmann fold, ferredoxin fold, ribonuclease H fold, and TIM β/α-barrel. On the basis of this classification system, we examined the shared substrate binding and catalytic mechanisms as well as variations of these mechanisms in the same fold groups. Cases of convergent evolution of identical kinase activities occurring in different folds are discussed.
AB - Kinases are a ubiquitous group of enzymes that catalyze the phosphoryl transfer reaction from a phosphate donor (usually ATP) to a receptor substrate. Although all kinases catalyze essentially the same phosphoryl transfer reaction, they display remarkable diversity in their substrate specificity, structure, and the pathways in which they participate. In order to learn the relationship between structural fold and functional specificities in kinases, we have done a comprehensive survey of all available kinase sequences (>17,000) and classified them into 30 distinct families based on sequence similarities. Of these families, 19, covering nearly 98% of all sequences, fall into seven general structural folds for which three-dimensional structures are known. These fold groups include some of the most widespread protein folds, such as Rossmann fold, ferredoxin fold, ribonuclease H fold, and TIM β/α-barrel. On the basis of this classification system, we examined the shared substrate binding and catalytic mechanisms as well as variations of these mechanisms in the same fold groups. Cases of convergent evolution of identical kinase activities occurring in different folds are discussed.
KW - Enzymes
KW - Fold
KW - Genomes
KW - Homology
KW - Protein classification
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U2 - 10.1016/S0022-2836(02)00538-7
DO - 10.1016/S0022-2836(02)00538-7
M3 - Article
C2 - 12095261
AN - SCOPUS:0036305943
SN - 0022-2836
VL - 320
SP - 855
EP - 881
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 4
ER -