Structure of apo, unactivated insulin-like growth factor-1 receptor kinase at 1.5 Å resolution

被引:60
作者
Munshi, S [1 ]
Hall, DL [1 ]
Kornienko, M [1 ]
Darke, PL [1 ]
Kuo, LC [1 ]
机构
[1] Merck Res Labs, Dept Biol Struct, West Point, PA 19486 USA
来源
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY | 2003年 / 59卷
关键词
D O I
10.1107/S0907444903015415
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The crystal structure of the wild-type unactivated kinase domain (IGFRK-0P) of insulin-like growth factor-1 receptor has been reported previously at 2.7 Angstrom resolution [Munshi et al. ( 2002), J. Biol. Chem. 277, 38797 - 38802]. In order to obtain a high-resolution structure, a number of variants of IGFRK-0P were prepared and screened for crystallization. A double mutant with E1067A and E1069A substitutions within the kinase-insert region resulted in crystals that diffracted to 1.5 Angstrom resolution. Overall, the structure of the mutant IGFRK-0P is similar to that of the wild-type IGFRK-0P structure, with the exception of the previously disordered kinase-insert region in the wild type having become fixed. In addition, amino-acid residues 947 - 952 at the N-terminus are well defined in the mutant structure. The monomeric protein structure is folded into two lobes connected by a hinge region, with the catalytic center situated at the interface of the two lobes. Two molecules of IGFRK-0P in the asymmetric unit are associated as a dimer and two different types of dimers with their ATP-binding clefts either facing towards or away from each other are observed. The current refined model consists of a dimer and 635 water molecules.
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收藏
页码:1725 / 1730
页数:6
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