Insights into protein kinase regulation and inhibition by large scale structural comparison.
Protein structure determination of soluble globular protein domains has developed into an efficient routine technology which can now be applied to generate and analyze structures of entire human protein families. In the kinase area, several kinase families still lack comprehensive structural analysis. Nevertheless, Structural Genomics (SG) efforts contributed more than 40 kinase catalytic domain structures during the past 4 years providing a rich resource of information for large scale comparisons of kinase active sites. Moreover, many of the released structures are inhibitor complexes that offer chemical starting points for development of selective and potent inhibitors. Here we discuss the currently available structural data and strategies that can be utilized for the development of highly selective inhibitors.
Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford Old Road Campus Building, Oxford OX3 7DQ, UK. jeyanthy.eswaran@sgc.ox.ac.uk
Jeyanthy
J
Eswaran
Stefan
S
Knapp
D000818:Animals; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases