Tyrosine structure

Taylor, S.S. Radzio-Andzelm, E. Hunter, T. How do protein kinases discriminate between serine/threonine and tyrosine Structural insights from the insulin receptor protein-tyrosine kinase. FASEB J., 9, 1255-1267 (1995)... 

This result suggests that the immune system tolerates a deviation from the natural structure occurring on the tumour cell surface only in a narrow window. In the case of 64 neither the glycosyl tyrosine structure nor the C-glycosidic linkage and the (3-anomer configuration match the natural structure. 

Zhang and co-workers worked on the structure-based, computer-assisted search for low molecular weight, non-peptidic protein tyrosine phosphate IB (PTPIB) inhibitors, also using the DOCK methodology [89], They identified several potent and selective PTPIB inhibitors by saeening the ACD. 

Above a pH of about 10 the major species present in a solution ] of tyrosine has a net charge of -2 Suggest a reasonable structure for this species J... 

The chemistry of the brain and central nervous system is affected by a group of substances called neurotransmitters, substances that carry messages across a synapse from one neuron to another Several of these neurotransmitters arise from l tyrosine by structural modification and decarboxylation as outlined m Figure 27 5... 

Figure 4.17 Schematic diagram of bound tyrosine to tyrosyl-tRNA synthetase. Colored regions correspond to van der Waals radii of atoms within a layer of the structure through the tyrosine ring. Red is bound tyrosine green is the end of P strand 2 and the beginning of the following loop region yellow is the loop region 189-192 and brown is part of the a helix in loop region 173-177.

C-terminal tail (Tyr 527 in c-Src). Phosphorylation of Tyr 419 activates the kinase phosphorylation of Tyr 527 inhibits it. Crystal structures of a fragment containing the last four domains of two members of this family were reported simultaneously in 1997—cellular Src by the group of Stephen Harrison and Hck by the group of John Kuriyan. The two structures are very similar, as expected since the 440 residue polypeptide chains have 60% sequence identity. The crucial C-proximal tyrosine that inhibits the activity of the kinases was phosphorylated in both cases the activation loop was not. 

Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.)...

C-terminal lobes of the tyrosine kinase are similar to those of cyclin-depen-dent kinase described in Chapter 6 (see Figure 6.16a), while the SH2 and SH3 domains of Src and Hck have structures very similar to those of the isolated domains (see Figures 13.26 and 13.28a). 

Figure 13.32 Regulation of the catalytic activity of members of the Src family of tyrosine kinases, (a) The inactive form based on structure determinations. Helix aC is in a position and orientation where the catalytically important Glu residue is facing away from the active site. The activation segment has a conformation that through steric contacts blocks the catalytically competent positioning of helix aC. (b) A hypothetical active conformation based on comparisons with the active forms of other similar protein kinases. The linker region is released from SH3, and the activation segment changes its structure to allow helix aC to move and bring the Glu residue into the active site in contact with an important Lys residue.

Src tyrosine kinase contains both an SH2 and an SH3 domain linked to a tyrosine kinase unit with a structure similar to other protein kinases. The phosphorylated form of the kinase is inactivated by binding of a phosphoty-rosine in the C-terminal tail to its own SH2 domain. In addition the linker region between the SH2 domain and the kinase is bound in a polyproline II conformation to the SH3 domain. These interactions lock regions of the active site into a nonproductive conformation. Dephosphorylation or mutation of the C-terminal tyrosine abolishes this autoinactivation. 

Sicheri, R, Moarefi, 1., Kuriyan, J. Crystal structure of the Src family tyrosine kinase Hck. Nature 385 602-609, 1997. 

Yamaguchi, H., Hendrickson, W. Structural basis for activation of human kinase Lck upon tyrosine phosphorylation. Nature 384 484-489, 1996. 

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