Sequence and structure classification of kinases

Sara Cheek, Hong Zhang, Nick V. Grishin

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)855-881
Number of pages27
JournalJournal of Molecular Biology
Volume320
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Phosphotransferases
Ribonuclease H
Ferredoxins
Substrate Specificity
Adenosine Triphosphate
Phosphates
Enzymes
Proteins

Keywords

  • Enzymes
  • Fold
  • Genomes
  • Homology
  • Protein classification

ASJC Scopus subject areas

  • Virology

Cite this

Sequence and structure classification of kinases. / Cheek, Sara; Zhang, Hong; Grishin, Nick V.

In: Journal of Molecular Biology, Vol. 320, No. 4, 2002, p. 855-881.

Research output: Contribution to journalArticle

Cheek, Sara ; Zhang, Hong ; Grishin, Nick V. / Sequence and structure classification of kinases. In: Journal of Molecular Biology. 2002 ; Vol. 320, No. 4. pp. 855-881.
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