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.
Highlights
Bruton's tyrosine kinase (Btk) belongs to the family of non receptor tyrosine kinases namely Tec family
PDB files of all the domains and Btk motif exists in protein data bank, this study considered some of them (Table 4) as multiple templates using Psi-Blast (Altschul et al, 1997), with matrix BLOSUM62 (Altschul et al, 2005)
Absence or abnormal Btk protein is responsible for the development of X-Linked Agammaglobulinemia (XLA) in humans
Summary
Bruton's tyrosine kinase (Btk) belongs to the family of non receptor tyrosine kinases namely Tec family. This is the second largest family of cytoplasmic protein tyrosine kinases and consists of five members; Btk, Itk, Tec, Rlk/Txk and Bmx. Btk is expressed in B cells and plays a crucial role in B-cell maturation and mast cell activation. Btk protein has C-terminal kinase domain followed by two Src homology domains (SH2 and SH3). At the N-terminal of the SH3 domain, Btk possesses two proline rich regions (PRR) with Zn2+-binding region known as Btk motif (BH). BH motif and the PRR together form the Tec homology domains. Btk possesses a pleckstrin homology domain (Lopez-Herrera et al, 2008).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
