Human kinome

Of the 517 protein kinases in the human kinome [116], structures are publicly available for < 10% of the different enzymes. In the absence of experimental data, construction of homology models based on known structures has proven a reliable method for generating 3D information. How, then, are the models built and what are the limitations of the models especially as applied to the family of protein kinases ... 

Figure 5. An example of intra-family target hopping within kinases. According to SiteSorter, Braf kinase, the primary target for the clinical compound BAY 43-9006, is one of the 10 most similar kinases to c-Kit, which has also been shown to bind BAY 43-9006 with sub-micromolar affinity (60% of the binding site residues are consen/ed and colored blue non-consen/ed positions are colored yellow). This cross-reactivity cannot be predicted based on the sequence similarity of the Braf and c-Kit kinase domains, since approximately one-sixth of the human kinome is more sequence similar to Braf than c-KiL...

The protein kinases in a proteome of an organism. See Manning, G., Whyle, D.B., Martinez, R., Hunter, T., and Sudarsanam, S., The protein kinase complanent of the human genome. Science 298,596-601,2(XX) ter Haar, E., Walters, W.P., Pazhanisamy, S. et al.. Kinase chemogenomics targeting the human kinome for target validation and drag discovery. Mini Rev. Med. Chem. 4, 235-253,2004. 

Fig. 8.2f-h), in good agreement with the de-wetting analysis. The dehydron matrix is precisely the representational tool that enables the simplest and fastest in silico assessment of drug cross-reactivity across the entire human kinome, as described in Chap. 9. 

Computational Tool Box for Comparative Analysis of Molecular Attributes Across the Human Kinome... 

The strong correlation shown in Fig. 9.2d provides compelling evidence in support of the universality of protein wrapping as the selectivity filter for molecular therapeutic approaches targeting the human kinome. 

There is strong evidence for the involvement of host (i.e. Human) cell kinases in the facilitation of the life cycle of the parasite. This is not surprising the parasite has evolved and adapted to its complicated life cycle and has presumably made use of the most efficient mechanism to drive its own proliferation, evade the host immune system, and preserve and protect those cells it has elected to grow within. Two recent studies have underscored this notion, and presented a number of host candidate kinases. The first study makes use of a collection of human kinome-related siRNAs to test their potential for reducing the proliferation of malaria parasites in human hepatocytes.41 Five host cell kinases were identified as being required for... 

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