Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS

被引:375
作者
Chou, KC
Wei, DQ
Zhong, WZ
机构
[1] Gordon Life Sci Inst, Kalamazoo, MI 49009 USA
[2] Tianjin Normal Univ, TIBDD, Tianjin, Peoples R China
关键词
SARS; coronavirus proteinase; KZ7088; AG7088; binding pocket; octapeptide substrate; distorted key" mechanism;
D O I
10.1016/S0006-291X(03)01342-1
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
In order to stimulate the development of drugs against severe acute respiratory syndrome (SARS), based on the atomic coordinates of the SARS coronavirus main proteinase determined recently [Science 13 (May) (2003) (online)], studies of docking KZ7088 (a derivative of AG7088) and the AVLQSGFR octapeptide to the enzyme were conducted. It has been observed that both the above compounds interact with the active site of the SARS enzyme through six hydrogen bonds. Also, a clear definition of the binding pocket for KZ7088 has been presented. These findings may provide a solid basis for subsite analysis and mutagenesis relative to rational design of highly selective inhibitors for therapeutic application. Meanwhile, the idea of how to develop inhibitors of the SARS enzyme based on the knowledge of its own peptide substrates (the so-called "distorted key" approach) was also briefly elucidated. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:148 / 151
页数:4
相关论文
共 10 条
  • [1] ANAND K, 2003, SCIENCE
  • [2] Prediction of human immunodeficiency virus protease cleavage sites in proteins
    Chou, KC
    [J]. ANALYTICAL BIOCHEMISTRY, 1996, 233 (01) : 1 - 14
  • [3] A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator
    Chou, KC
    Watenpaugh, KD
    Heinrikson, RL
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 259 (02) : 420 - 428
  • [4] Prediction of the tertiary structure of a caspase-9/inhibitor complex
    Chou, KC
    Tomasselli, AG
    Heinrikson, RL
    [J]. FEBS LETTERS, 2000, 470 (03) : 249 - 256
  • [5] Prediction of the tertiary structure of the β-secretase zymogen
    Chou, KC
    Howe, WJ
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 292 (03) : 702 - 708
  • [6] CHOU KC, 1993, J BIOL CHEM, V268, P16938
  • [7] STRUCTURE OF COMPLEX OF SYNTHETIC HIV-1 PROTEASE WITH A SUBSTRATE-BASED INHIBITOR AT 2.3-A RESOLUTION
    MILLER, M
    SCHNEIDER, J
    SATHYANARAYANA, BK
    TOTH, MV
    MARSHALL, GR
    CLAWSON, L
    SELK, L
    KENT, SBH
    WLODAWER, A
    [J]. SCIENCE, 1989, 246 (4934) : 1149 - 1152
  • [8] ON SIZE OF ACTIVE SITE IN PROTEASES .I. PAPAIN
    SCHECHTER, I
    BERGER, A
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1967, 27 (02) : 157 - +
  • [9] Structure and regulation of the CDK5-p25nck5a complex
    Tarricone, C
    Dhavan, R
    Peng, JM
    Areces, LB
    Tsai, LH
    Musacchio, A
    [J]. MOLECULAR CELL, 2001, 8 (03) : 657 - 669
  • [10] Identification of the N-terminal functional domains of Cdk5 by molecular truncation and computer modeling
    Zhang, JW
    Luan, CH
    Chou, KC
    Johnson, GVW
    [J]. PROTEINS-STRUCTURE FUNCTION AND GENETICS, 2002, 48 (03): : 447 - 453