SOLUTION STRUCTURE OF THE CAMP-DEPENDENT PROTEIN-KINASE CATALYTIC SUBUNIT AND ITS CONTRACTION UPON BINDING THE PROTEIN-KINASE INHIBITOR PEPTIDE

被引:73
|
作者
OLAH, GA
MITCHELL, RD
SOSNICK, TR
WALSH, DA
TREWHELLA, J
机构
[1] LOS ALAMOS NATL LAB, DIV ISOTOPE & NUCL CHEM, LOS ALAMOS, NM 87545 USA
[2] UNIV CALIF DAVIS, DEPT BIOL CHEM, DAVIS, CA 95616 USA
关键词
D O I
10.1021/bi00065a018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Small-angle X-ray scattering and Fourier transform infrared (FTIR) spectroscopy experiments have been completed on the catalytic subunit of the cAMP-dependent protein kinase. Measurements were made both with and without the protein kinase inhibitor peptide, PKIalpha(5-22)amide. Binding of the peptide results in an overall contraction of the structure that is characterized by a decrease of 9% in radius of gyration and about 16% in the maximum linear dimension. Both the secondary structure content of the protein/peptide complex, as determined by FTIR, and the solution structure of this binary complex, as determined by X-ray scattering, agree well with the structural characteristics of this complex as elucidated by the crystal structure [Knighton, D. R., Zheng, J., Ten Eyck, L. F., Ashford, V. A., Xuong, N.- H., Taylor, S.S., & Sowadsi, J.M. (1991a) Science 253, 407-414]. Further, the contraction of the structure observed by X-ray scattering upon inhibitor peptide binding is not accompanied by any detectable change in secondary structure content of the kinase. We have modeled the contraction of the kinase upon inhibitor peptide binding as a simple rotation of the large and small lobes seen in the crystal structure such that the cleft between them is closed. For a substrate these changes would then allow catalysis to ensue. The hinge for this movement occurs around a glycine that is one of the protein kinase family consensus amino acids.
引用
收藏
页码:3649 / 3657
页数:9
相关论文
共 50 条
  • [41] REGULATORY SUBUNIT OF THE TYPE-I CAMP-DEPENDENT PROTEIN-KINASE AS AN INHIBITOR AND SUBSTRATE OF THE CGMP-DEPENDENT PROTEIN-KINASE
    GEAHLEN, RL
    KREBS, EG
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1980, 255 (03) : 1164 - 1169
  • [42] CRYSTAL-STRUCTURES OF THE CATALYTIC SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE REVEAL GENERAL FEATURES OF THE PROTEIN-KINASE FAMILY
    TAYLOR, SS
    RADZIOANDZELM, E
    KNIGHTON, DR
    TENEYCK, LF
    SOWADSKI, JM
    HERBERG, FW
    YONEMOTO, W
    ZHENG, JH
    RECEPTOR, 1993, 3 (03) : 165 - 172
  • [43] INHIBITOR PROTEIN OF THE CAMP-DEPENDENT PROTEIN-KINASE - CHARACTERISTICS AND PURIFICATION
    WHITEHOUSE, S
    WALSH, DA
    METHODS IN ENZYMOLOGY, 1983, 99 : 80 - 93
  • [44] MG.ATP2--DEPENDENT INTERACTION OF THE INHIBITOR PROTEIN OF THE CAMP-DEPENDENT PROTEIN-KINASE WITH THE CATALYTIC SUBUNIT
    WHITEHOUSE, S
    WALSH, DA
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1983, 258 (06) : 3682 - 3692
  • [45] SYNTHETIC PEPTIDE SUBSTRATES OF CAMP-DEPENDENT PROTEIN-KINASE
    KEMP, BE
    GRAVES, DJ
    BENJAMINI, E
    FEDERATION PROCEEDINGS, 1976, 35 (07) : 1384 - 1384
  • [46] THERMOSTABLE INHIBITOR OF CAMP-DEPENDENT PROTEIN-KINASE ENHANCES THE RATE OF EXPORT OF THE KINASE CATALYTIC SUBUNIT FROM THE NUCLEUS
    FANTOZZI, DA
    HAROOTUNIAN, AT
    WEN, W
    TAYLOR, SS
    FERAMISCO, JR
    TSIEN, RY
    MEINKOTH, JL
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1994, 269 (04) : 2676 - 2686
  • [47] CATALYSIS IN CAMP-DEPENDENT PROTEIN-KINASE
    ADAMS, JA
    MCGLONE, ML
    TAYLOR, SS
    FASEB JOURNAL, 1994, 8 (07): : A1238 - A1238
  • [48] DROSOPHILA CAMP-DEPENDENT PROTEIN-KINASE
    FOSTER, JL
    GUTTMANN, J
    HALL, LM
    ROSEN, OM
    FEDERATION PROCEEDINGS, 1983, 42 (07) : 2254 - 2254
  • [49] DROSOPHILA CAMP-DEPENDENT PROTEIN-KINASE
    FOSTER, JL
    GUTTMAN, JJ
    HALL, LM
    ROSEN, OM
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1984, 259 (21) : 3049 - 3055
  • [50] INJECTION OF CATALYTIC SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE INTO ISOLATED CARDIAC MYOCYTES
    BRUM, G
    FLOCKERZI, V
    HOFMANN, F
    OSTERRIEDER, W
    TRAUTWEIN, W
    PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1983, 398 (02): : 147 - 154