Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors.
In this article, we report crystal structures for inhibitor-kinase complexes in which the inhibitor has different binding orientations and hydrogen-bonding patterns with extracellular-signal regulated kinase 2 and insulin receptor tyrosine kinase. Our crystallographic studies, and sequence and structural analyses of 532 coordinates of kinases held in the Protein Data Bank, suggest that the length of the "specificity linker" described here is a key structural element of the hydrogen-bonding patterns between protein kinases and their inhibitors.
Katayama
Naoko
N
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Orita
Masaya
M
Yamaguchi
Tomohiko
T
Hisamichi
Hiroyuki
H
Kuromitsu
Sadao
S
Kurihara
Hiroyuki
H
Sakashita
Hitoshi
H
Matsumoto
Yuzo
Y
Fujita
Shigeo
S
Niimi
Tatsuya
T