Abstract

Bruton's tyrosine kinase (Btk), a member of non-receptor tyrosine kinases, is one of the crucial kinases for the B-cell maturation and mast cell activation. This work was planned to develop the full length Btk protein structure via different approaches. The threading approach provided suitable full length Btk protein structure. Furthermore, this structure was utilized to predict the consequences of 16 selected missense mutations in the kinase domain (402 to 651) around Y551, a first tyrosine to be autophosphorylated and important for downstream signaling. Valuable information gathered from this work is an insight for analyzing protein structural changes and their effects on protein stability. The amino acid residues at positions 554, 559 and 562 were considered critical as per their involvement and presence near the catalytic site, peptide substrate binding pocket and their linkage with other amino acid residues resulting in the disturbance of structural integrity.

Key words: Bruton's tyrosine kinase (Btk), in silico, kinase domain, comparative homology modeling, autophosphorylation.

Abbreviation

Btk, Bruton's tyrosine kinase; SH, Src homology; PH, pleckstrin homology; NCBI, National Center for Biotechnology Information; PDB, protein data bank; aa, amino acid; PTK, protein tyrosine kinase; Y, tyrosine.