GS4071 is a slow-binding inhibitor of influenza neuraminidase from both A and B strains

被引:40
作者
Kati, WM
Saldivar, AS
Mohamadi, F
Sham, HL
Laver, WG
Kohlbrenner, WE
机构
[1] Abbott Labs, Dept 47D, Infect Dis Res, Abbott Pk, IL 60064 USA
[2] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia
关键词
D O I
10.1006/bbrc.1998.8282
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
The kinetics of inhibition of purified influenza neuraminidases hom A/Tokyo/3/67 and B/Memphis/3/89 influenza viruses by (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene- 1-carboxylic acid (GS4071) were investigated. Progress curve experiments established that GS4071 is a time dependent inhibitor of both A and B strains of influenza neuraminidase. The apparent association and dissociation rate constants, as well as the overall Ki values, were only modestly different for the two neuraminidase strains. The time dependent inhibition phenomenon, often referred to as slow-binding inhibition, appears to be a consequence of the very slow rate of dissociation of the compound from influenza neuraminidase. (C) 1998 Academic Press.
引用
收藏
页码:408 / 413
页数:6
相关论文
共 27 条
[1]   ANTIGENIC, SEQUENCE, AND CRYSTAL VARIATION IN INFLUENZA-B NEURAMINIDASE [J].
AIR, GM ;
LAVER, WG ;
LUO, M ;
STRAY, SJ ;
LEGRONE, G ;
WEBSTER, RG .
VIROLOGY, 1990, 177 (02) :578-587
[2]   3-DIMENSIONAL STRUCTURE OF INFLUENZA-A N9 NEURAMINIDASE AND ITS COMPLEX WITH THE INHIBITOR 2-DEOXY 2,3-DEHYDRO-N-ACETYL NEURAMINIC ACID [J].
BOSSARTWHITAKER, P ;
CARSON, M ;
BABU, YS ;
SMITH, CD ;
LAVER, WG ;
AIR, GM .
JOURNAL OF MOLECULAR BIOLOGY, 1993, 232 (04) :1069-1083
[3]   THE 2.2-A RESOLUTION CRYSTAL-STRUCTURE OF INFLUENZA-B NEURAMINIDASE AND ITS COMPLEX WITH SIALIC-ACID [J].
BURMEISTER, WP ;
RUIGROK, RWH ;
CUSACK, S .
EMBO JOURNAL, 1992, 11 (01) :49-56
[4]  
Colman P.M., 1989, INFLUENZA VIRUSES, P175
[5]   AVIDIN IS A SLOW-BINDING INHIBITOR OF PYRUVATE-CARBOXYLASE [J].
DUGGLEBY, RG ;
ATTWOOD, PV ;
WALLACE, JC ;
KEECH, DB .
BIOCHEMISTRY, 1982, 21 (14) :3364-3370
[6]  
FERSHT A, 1985, ENZYME STRUCTURE MEC, P139
[7]   ADENOSINE-DEAMINASE AND ADENYLATE DEAMINASE - COMPARATIVE KINETIC-STUDIES WITH TRANSITION-STATE AND GROUND-STATE ANALOG INHIBITORS [J].
FRIEDEN, C ;
KURZ, LC ;
GILBERT, HR .
BIOCHEMISTRY, 1980, 19 (23) :5303-5309
[8]  
Hart GJ, 1995, BIOCHEM MOL BIOL INT, V36, P695
[9]   STRUCTURE OF INFLUENZA-VIRUS NEURAMINIDASE B/LEE/40 COMPLEXED WITH SIALIC-ACID AND A DEHYDRO ANALOG AT 1.8-ANGSTROM RESOLUTION - IMPLICATIONS FOR THE CATALYTIC MECHANISM [J].
JANAKIRAMAN, MN ;
WHITE, CL ;
LAVER, WG ;
AIR, GM ;
LUO, M .
BIOCHEMISTRY, 1994, 33 (27) :8172-8179
[10]   Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: Design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity [J].
Kim, CU ;
Lew, W ;
Williams, MA ;
Liu, HT ;
Zhang, LJ ;
Swaminathan, S ;
Bischofberger, N ;
Chen, MS ;
Mendel, DB ;
Tai, CY ;
Laver, WG ;
Stevens, RC .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (04) :681-690