Kinase superfamily

This protein kinase (known as protein kinase A or PK-A) has an R2C2 quaternary structure that binds 3, 5 -cAMP at its dimeric regulatory (R) subunit with resultant release of two catalytic (C) subunits. The free energy of hydrolysis of the cychc nucleotide activator is large (AG 13 kcal/mol) and allows the 3, 5 -cAMP to be virtually irreversibly converted to AMP by the action of a specific phosphodiesterase. This protein kinase, originally discovered by the Nobelists Edwin Krebs and Edward Fischer, is now considered to be the prototype for over two thousand members of the protein kinase superfamily. 

Romanowski, M.J. Bonanno, J.B. Burley, S.K. Crystal structure of the Streptococcus pneumoniae phosphomevalonate kinase, a member of the GHMP kinase superfamily. Proteins Struct. Fund. Genet., 47, 568-571 (2002)... 

Hanks SK, Hunter T (1995) Protein kinases 6. The eukaryotic protein kinase superfamily kinase (catalytic) domain structure and classification. FASEB J 9 576-596... 

Igarashi, M., A. Hirata, H. Yamaguchi, N. Sugae, Y. Kadomoto-Antsuki, H. Nozaki, Y. Jimbu, and M. Tominaga. 2007. Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats. J. Atheroscler. Thromb. 14 235-244. 

Zhou T, Daugherty M, Grishin NV et al (2000) Structure and mechanism ofhomoserine kinase prototype for the GHMP kinase superfamily. Structure 8 1247-1257... 

Hanks SK (2003) Genomic analysis of the eukaryotic protein kinase superfamily a perspective. Genome Biol 4(5) 111... 

The kinase superfamily consists of numerous kinases that have a common folding pattern. Therefore, it is generally difficult to improve the target kinase selectivity with respect to all the other kinases at the same time. However, protein kinases play various important roles in the human body, and they are also very attractive targets for drug discovery. We believe that this approach should be useful for the more systematic and efficient development of highly specific kinase inhibitors. 

M. Bowker-Kinley and K.M. Popov. 1999. Evidence that pyruvate dehydrogenase kinase belongs to the ATPase/kinase superfamily Biochem. J. 1 47-53. 

Besides giving the level of conservation of each packing defect, the library should provide an assessment of the expected cross-reactivity for a dmg that wraps the defect. As a concrete example, let us determine the level of control of crossreactivity that may be achieved when wrapping the KIT dehydron C673-G676, as described in Chap. 8. Table 9.1 provides a comparative analysis of the conservation of the KIT dehydron across KIT paralogs and other members of the kinase superfamily. 

In addition to the MAP kinases discussed above, both yeasts and higher eukaryotic cells contain other members of the MAP kinase superfamily. These Include mammalian Jun N-terminal kinases (JNKs) and p38 kinases, which become activated by various types of stresses, and six yeast kinases described below. Collectively referred to as MAP kinases, all these proteins are serlne/threonlne kinases that are activated in the cytosol in response to specific extracellular signals and then translocate to the nucleus. Activation of all known MAP kinases requires phosphorylation of both a tyrosine and a... 

ATR, ATM, DNA-PK (s.c. MEGl, TELl s.p. Rad3) Protein kinase of the PI3-kinase superfamily, Phosphorylates target substrates at SQ or TQ motifs Master switch... 

D Aniello S, Irimia M, Maeso 1, Pascual-Anaya J, Jimenez-Delgado S, Bertrand S, Garcia-Femandez J. Gene expansion and retention leads to a diverse tyrosine kinase superfamily in amphioxus. Mol Biol Evol. 2008 25 1841-54. 

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