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Related Experiment Videos

Sequence and structure classification of kinases.

Sara Cheek1, Hong Zhang, Nick V Grishin

  • 1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.

Journal of Molecular Biology
|July 4, 2002
PubMed
Summary

This study classifies over 17,000 kinase sequences into 30 families, revealing that 19 families share seven common structural folds. This reveals links between kinase structure and function.

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Enzymology

Background:

  • Kinases are crucial enzymes catalyzing phosphoryl transfer, primarily from ATP.
  • Despite a conserved core reaction, kinases exhibit vast diversity in substrate specificity, structure, and biological pathways.
  • Understanding the link between structural fold and functional specificity is key to kinase research.

Purpose of the Study:

  • To comprehensively survey and classify all available kinase sequences.
  • To investigate the relationship between structural folds and functional specificities in kinases.
  • To analyze shared and varied substrate binding and catalytic mechanisms within kinase fold groups.

Main Methods:

  • Performed a comprehensive sequence similarity survey of over 17,000 kinase sequences.

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  • Classified kinases into 30 distinct families based on sequence similarities.
  • Mapped kinase families to known three-dimensional structural folds.
  • Main Results:

    • Identified 30 distinct kinase families, with 19 families (98% of sequences) belonging to seven general structural folds.
    • These folds include widespread types like Rossmann, ferredoxin, ribonuclease H, and TIM beta/alpha-barrel.
    • Examined conserved and divergent substrate binding and catalytic mechanisms across different fold groups.

    Conclusions:

    • Kinase classification based on sequence similarity reveals a strong correlation with structural folds.
    • Structural folds provide a framework for understanding conserved and varied kinase functions.
    • Identified instances of convergent evolution where identical kinase activities evolved in different structural folds.