Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis

被引:594
作者
Belisle, JT [1 ]
Vissa, VD [1 ]
Sievert, T [1 ]
Takayama, K [1 ]
Brennan, PJ [1 ]
Besra, GS [1 ]
机构
[1] UNIV WISCONSIN, WILLIAM S MIDDLETON MEM VET HOSP, MYCOBACTERIOL RES LAB, MADISON, WI 53705 USA
关键词
D O I
10.1126/science.276.5317.1420
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The dominant exported proteins and protective antigens of Mycobacterium tuberculosis are a triad of related gene products called the antigen 85 (Ag85) complex. Each has also been implicated in disease pathogenesis through its fibronectin-binding capacities, A carboxylesterase domain was found within the amino acid sequences of Ag85A, B, and C, and each protein acted as a mycolyltransferase involved in the final stages of mycobacterial cell wall assembly, as shown by direct enzyme assay and site-directed mutagenesis. Furthermore, the use of an antagonist (6-azido-6-deoxy-alpha,alpha'-trehalose) of this activity demonstrates that these proteins are essential and potential targets for new antimycobacterial drugs.
引用
收藏
页码:1420 / 1422
页数:3
相关论文
共 32 条
  • [1] IDENTIFICATION OF THE APPARENT CARRIER IN MYCOLIC ACID SYNTHESIS
    BESRA, GS
    SIEVERT, T
    LEE, RE
    SLAYDEN, RA
    BRENNAN, PJ
    TAKAYAMA, K
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (26) : 12735 - 12739
  • [2] Molecular mechanisms of drug resistance in Mycobacterium tuberculosis
    Blanchard, JS
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 : 215 - 239
  • [3] BRENNAN PJ, 1995, ANNU REV BIOCHEM, V64, P63
  • [4] HIGH-THROUGHPUT SCREEN FOR DETECTING ANTIMYCOBACTERIAL AGENTS
    CHUNG, GAC
    AKTAR, Z
    JACKSON, S
    DUNCAN, K
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (10) : 2235 - 2238
  • [5] CRYSTAL-STRUCTURE AND FUNCTION OF THE ISONIAZID TARGET OF MYCOBACTERIUM-TUBERCULOSIS
    DESSEN, A
    QUEMARD, A
    BLANCHARD, JS
    JACOBS, WR
    SACCHETTINI, JC
    [J]. SCIENCE, 1995, 267 (5204) : 1638 - 1641
  • [6] EVIDENCE FOR GLYCOSYLATION SITES ON THE 45-KILODALTON GLYCOPROTEIN OF MYCOBACTERIUM-TUBERCULOSIS
    DOBOS, KM
    SWIDEREK, K
    KHOO, KH
    BRENNAN, PJ
    BELISLE, JT
    [J]. INFECTION AND IMMUNITY, 1995, 63 (08) : 2846 - 2853
  • [7] DUNBAR BS, 1990, METHOD ENZYMOL, V182, P441
  • [8] THE BIOSYNTHESIS OF CYCLOPROPANATED MYCOLIC ACIDS IN MYCOBACTERIUM-TUBERCULOSIS - IDENTIFICATION AND FUNCTIONAL-ANALYSIS OF CMAS-2
    GEORGE, KM
    YUAN, Y
    SHERMAN, DR
    BARRY, CE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (45) : 27292 - 27298
  • [9] SYNTHESIS OF 6-AMINO-6-DEOXY-ALPHA,ALPHA-TREHALOSE - POSITIONAL ISOMER OF TREHALOSAMINE
    HANESSIAN, S
    LAVALLEE, P
    [J]. JOURNAL OF ANTIBIOTICS, 1972, 25 (11) : 683 - +
  • [10] HIGGINS DG, 1992, COMPUT APPL BIOSCI, V8, P189