Toward understanding the mechanism of the complex cyclization reaction catalyzed by imidazole glycerolphosphate synthase: Crystal structures of a ternary complex and the free enzyme

被引:60
作者
Chaudhuri, BN
Lange, SC
Myers, RS
Davisson, VJ
Smith, JL [1 ]
机构
[1] Purdue Univ, Dept Biol Sci, 915 W State St, W Lafayette, IN 47907 USA
[2] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA
关键词
D O I
10.1021/bi034320h
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
Imidazole glycerol phosphate synthase catalyzes formation of the imidazole ring in histidine biosynthesis. The enzyme is also a glutamine amidotransferase, which produces ammonia in a glutaminase active site and channels it through a 30-Angstrom internal tunnel to a cyclase active site. Glutaminase activity is impaired in the resting enzyme, and stimulated by substrate binding in the cyclase active site. The signaling mechanism was investigated in the crystal structure of a ternary complex in which the glutaminase active site was inactivated by a glutamine analogue and the unstable cyclase substrate was cryo-trapped in the active site. The orientation of N-1-(5'-phosphoribulosyl)-formimino-5-aminoimidazole-4-carboxamide ribonucleotide in the cyclase active site implicates one side of the cyclase domain in signaling to the glutaminase domain. This side of the cyclase domain contains the interdomain hinge. Two interdomain hydrogen bonds, which do not exist in more open forms of the enzyme, are proposed as molecular signals. One hydrogen bond connects the cyclase domain to the substrate analogue in the glutaminase active site. The second hydrogen bond connects to a peptide that forms an oxyanion hole for stabilization of transient negative charge during glutamine hydrolysis. Peptide rearrangement induced by a fully closed domain interface is proposed to activate the glutaminase by unblocking the oxyanion hole. This interpretation is consistent with biochemical results [Myers, R. S., et al., (2003) Biochemistry 42, 7013-7022, the accompanying paper in this issue] and with structures of the free enzyme and a binary complex with a second glutamine analogue.
引用
收藏
页码:7003 / 7012
页数:10
相关论文
共 41 条
  • [1] Histidine biosynthetic pathway and genes: Structure, regulation, and evolution
    Alifano, P
    Fani, R
    Lio, P
    Lazcano, A
    Bazzicalupo, M
    Carlomagno, MS
    Bruni, CB
    [J]. MICROBIOLOGICAL REVIEWS, 1996, 60 (01) : 44 - +
  • [2] Allen F.H., 1993, CHEM AUTOMAT NEWS, V8, P31
  • [3] Structure of HisF, a histidine biosynthetic protein from Pyrobaculum aerophilum
    Banfield, MJ
    Lott, JS
    Arcus, VL
    McCarthy, AA
    Baker, EN
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2001, 57 : 1518 - 1525
  • [4] Imidazole glycerol phosphate synthase from Thermotoga maritima -: Quaternary structure, steady-state kinetics, and reaction mechanism of the bienzyme complex
    Beismann-Driemeyer, S
    Sterner, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (23) : 20387 - 20396
  • [5] Temperature-dependent function of the glutamine phosphoribosylpyrophosphate amidotransferase ammonia channel and coupling with glycinamide ribonucleotide synthetase in a hyperthermophile
    Bera, AK
    Chen, S
    Smith, JL
    Zalkin, H
    [J]. JOURNAL OF BACTERIOLOGY, 2000, 182 (13) : 3734 - 3739
  • [6] PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES
    BERNSTEIN, FC
    KOETZLE, TF
    WILLIAMS, GJB
    MEYER, EF
    BRICE, MD
    RODGERS, JR
    KENNARD, O
    SHIMANOUCHI, T
    TASUMI, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1977, 112 (03) : 535 - 542
  • [7] SLOW-COOLING PROTOCOLS FOR CRYSTALLOGRAPHIC REFINEMENT BY SIMULATED ANNEALING
    BRUNGER, AT
    KRUKOWSKI, A
    ERICKSON, JW
    [J]. ACTA CRYSTALLOGRAPHICA SECTION A, 1990, 46 : 585 - 593
  • [8] Crystallography & NMR system:: A new software suite for macromolecular structure determination
    Brunger, AT
    Adams, PD
    Clore, GM
    DeLano, WL
    Gros, P
    Grosse-Kunstleve, RW
    Jiang, JS
    Kuszewski, J
    Nilges, M
    Pannu, NS
    Read, RJ
    Rice, LM
    Simonson, T
    Warren, GL
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 : 905 - 921
  • [9] Crystal structure of imidazole glycerol phosphate synthase:: A tunnel through a (β/α)8 barrel joins two active sites
    Chaudhuri, BN
    Lange, SC
    Myers, RS
    Chittur, SV
    Davisson, VJ
    Smith, JL
    [J]. STRUCTURE, 2001, 9 (10) : 987 - 997
  • [10] Tryptophan fluorescence monitors multiple conformational changes required for glutamine phosphoribosylpyrophosphate amidotransferase interdomain signaling and catalysis
    Chen, SH
    Burgner, JW
    Krahn, JM
    Smith, JL
    Zalkin, H
    [J]. BIOCHEMISTRY, 1999, 38 (36) : 11659 - 11669