Tyrosine identification

Peng H, Huang N, Qi J, Xie P, Xn C, Wang J, Yang C. Identification of novel inhibitors of BCR-ABL tyrosine kinase via virtnal screening. Bioorg Med Chem Lett 2003 13 3693-9. 

Humans can synthesize 12 of the 20 common amino acids from the amphiboHc intermediates of glycolysis and of the citric acid cycle (Table 28-1). While nutritionally nonessenrial, these 12 amino acids are not nonessential. AH 20 amino acids are biologically essential. Of the 12 nutritionally nonessential amino acids, nine are formed from amphibolic intermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionally essential amino acids. Identification of the twelve amino acids that humans can synthesize rested primarily on data derived from feeding diets in which purified amino acids replaced protein. This chapter considers only the biosynthesis of the twelve amino acids that are synthesized in human tissues, not the other eight that are synthesized by plants. 

Other PTMs may involve changes in the chemical nature of amino acids (e.g., citrullination or deimination). Because many of these modifications result in mass changes that are measurable by MS, they are amenable to detection by MS-based approaches. A number of emerging MS-based strategies allow the identification of PTMs. Several MS-based methods to determine the types and sites of protein phosphorylation and ubiquitination have been developed. Phosphorylation occurs mainly on serine, threonine, and tyrosine residues at a frequency ratio of 1800 200 1 in vertebrates.70 Although the phosphorylation of tyrosine residues occurs less frequently in the proteome, it has been extensively studied. 

Prioleau, C., Visiers, I., Ebersole, B. J., Weinstein, H., and Sealfon, S. (2002) Conserved helix7 tyrosine acts as a multistate conformational switch in the 5-HT2C receptor Identification of a novel locked-on phenotype and double revertant mutations. J. Biol. Chem. 277, 36577-36584. 

O Malley KL, Anhalt MJ, Martin BM, Kelsoe JR, Winfield SL, et al. 1987. Isolation and characterization of the human tyrosine hydroxylase gene identification of 5 alternative splice sites responsible for multiple mRNAs. Biochemistry 26 6910-6914. 

Another milestone in this research area was the isolation and identification of antigens from tumor tissue [e.g., tyrosine-related proteins (TRP)-1 and (TRP)-2]. After the administration of these antigens, it became clear that a sufficient success was only possible by the concomitant administration of adjuvant-acting substances like CpG-oligonucleotides (8). 

N. Frontal affinity chromatography with MS detection of EphB2 tyrosine kinase receptor. 2. Identification of small-molecule inhibitors via coupling with virtual screening. J Med Chem 2005, 48, 3221-3230. 

Resonance Raman studies of Fe- and Cu-contalnlng proteins have led to the Identification of tyrosine, histidine, cysteine, and hydroxide ligands as well as Fe-0 and Fe-S clusters. For the Fe-0 clusters, the frequency and oxygen Isotope dependence of the Fe-O-Fe symmetric stretch relates to Fe-O-Fe bond angle, while the peak Intensity relates to the disposition of the other ligands In the cluster. 

Zheng, F. F., S. D. Kuduk, G. Chiosis, P. N. Munster, L. Sepp-Lorenzino, S. J. Danishefsky, and N. Rosen. Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases. Cancer Res. 60 2090-4.2000a. 

The signaling mechanisms activated by neurotrophic factors, which include nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are fundamentally different from those discussed for G protein-coupled receptors and Ca " (Russell and Duman 2002). The neurotrophic factors bind to specific receptors, TrkA, TrkB, and TrkC (the name Trk is derived from their identification as troponin/receptor kinases from colon carcinoma) (Fig. 2). The Trk receptors contain an extracellular binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. Two neurotrophic factor molecules are required for activation of a Trk receptor dimer, resulting in activation of the tyrosine kinase domains and phosphorylation of substrate proteins as well as autophosphorylation of the Trk receptor itself. 

For the analytical characterization of sulfated tyrosine peptides, spectroscopic methods as well as amino acid analysis and, more recently, mass spectrometry are employed. In Table 2 the spectroscopic data of tyrosine 0-sulfate are compared to those of the related sulfonic acid derivatives as possible byproducts in the chemical sulfation of the tyrosine or tyrosine peptides.[361 In the course of the synthesis of tyrosine 0-sulfate peptides and, particularly in the final deprotection step, desulfation may occur which limits the characterization of the final compounds in terms of quantitative identification of the tyrosine 0-sulfate. This is achieved by amino acid analyses of basic hydrolysates of the sulfated tyrosine peptides or preferably by analyses of the enzymatic hydrolysates with aminopeptidase M or leucine-aminopeptidase. 

Janing, G. R., Kraft, R., Blanck, J., Rabe, H., and Ruckpaul, K. (1987). Chemical modification of cytochrome P-450 LM4. Identification of functionally linked tyrosine residues. Biochim. Biophys. Acta. 916, 512-523. 

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