Structural comparisons of class I phosphoinositide 3-kinases.
Class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that regulate cell growth. One of these kinases, PI3Kalpha, is frequently mutated in diverse tumour types. The recently determined structure of PI3Kalpha reveals features that distinguish this enzyme from related lipid kinases. In addition, wild-type PI3Kgamma differs from PI3Kalpha by a substitution identical to a PI3Kalpha oncogenic mutant (His1047Arg) that might explain the differences in the enzymatic activities of the normal and mutant PI3Kalpha. Comparison of the PI3K structures also identified structural features that could potentially be exploited for the design of isoform-specific inhibitors.
Amzel
L Mario
LM
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Huang
Chuan-Hsiang
CH
Mandelker
Diana
D
Lengauer
Christoph
C
Gabelli
Sandra B
SB
Vogelstein
Bert
B
D058544:Class Ib Phosphatidylinositol 3-Kinase; D007527:Isoenzymes / Q000737:chemistry; D008958:Models, Molecular; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000235:genetics; D017434:Protein Structure, Tertiary
D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D058544:Class Ib Phosphatidylinositol 3-Kinase