THE CRYSTAL-STRUCTURE OF HUMAN CSKSH3 - STRUCTURAL DIVERSITY NEAR THERT-SRC AND N-SRC LOOP

SH3 domains are modules occurring in diverse proteins, ranging from cy toskeletal proteins to signaling proteins, such as tyrosine kinases. T he crystal structure of the SH3 domain of Csk (c-Src specific tyrosine kinase) has been refined at a resolution of 2.5 Angstrom, with an R-f actor of 22.4%. The structure is very similar to the FynSH3 crystal st ructure. When comparing CskSH3 and FynSH3 it is seen that the structur al and charge differences of the RT-Src loop and the n-Src loop, near the conserved Trp(47), correlate with different binding properties of these SH3 domains. The structure comparison suggests that those glycin es and acid residues which are very well conserved in the SH3 sequence s are important for the stability of the SH3 fold.