Open AccessDomain identification by iterative analysis of error‐scaled difference distance matrices
Author(s) -
Schneider Thomas R.
Publication year - 2004
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444904023492
Subject(s) - sh3 domain , proto oncogene tyrosine protein kinase src , residue (chemistry) , domain (mathematical analysis) , protein kinase domain , sh2 domain , crystallography , kinase , chemistry , mathematics , biochemistry , mathematical analysis , mutant , gene
Iterative interpretation of error‐scaled difference distance matrices is suggested as a means of dividing a protein into structural domains on the basis of conformational differences between different models. Two conformers of Src kinase {PDB codes 1fmk [Xu et al. (1997). Nature (London) , 385 , 595–602] and 2src [Xu et al. (1999). Mol. Cell , 3 , 629–638]} in the inactive state with and without a substrate analogue bound are analysed in order to demonstrate the approach. SH3, SH2 and the N‐ and C‐terminal lobes of the kinase domain are detected as structural modules that move with respect to each other. Notably, a relative movement between the SH3 and SH2 domains is detected although both structures of Src kinase are in the `assembled' state. Detailed analysis shows that Arg318, a residue topologically located in the N‐terminal lobe of the kinase domain, structurally belongs to the C‐terminal lobe. The movement of this residue together with the C‐terminal lobe upon substrate binding leads to the loss of a salt bridge between Arg318 and Asp117, a residue in the SH3 domain, providing an explanation for the increased mobility of the SH3 domain.