H-1 AND N-15 ASSIGNMENTS AND SECONDARY STRUCTURE OF THE PI3K-SH3 DOMAIN

The sequential H-1 and N-15 assignments of the SH3 domain of human pho sphatidyl inositol 3'-kinase (PI3K) were determined by a combination o f homonuclear and heteronuclear NMR experiments. With the exception of several protons belonging to lysine and proline residues, all proton and proton-bearing amide nitrogen resonances were assigned. Based on t he sequential nuclear Overhauser effects (NOEs), 3J(NH-CalphaH) coupli ng constants and locations of slowly exchanging amide protons, we dete rmined that the secondary structures of the protein consists of six be ta-strands, two beta-turns and four short helices. Additional long ran ge NOEs indicate that these beta-strands form two antiparallel beta-sh eets. The topology of secondary structural elements of the PI3K SH3 do main is similar to those of the SH3 domains from c-Src and alpha-spect rin, suggesting that the SH3 family has a common tertiary structural m otif.