Recent advances in the structure and function of isopenicillin N synthase

被引:17
作者
Kreisberg-Zakarin, R [1 ]
Borovok, I [1 ]
Yanko, M [1 ]
Aharonowitz, Y [1 ]
Cohen, G [1 ]
机构
[1] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-69978 Ramat Aviv, Israel
来源
ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY | 1999年 / 75卷 / 1-2期
基金
以色列科学基金会;
关键词
active site; crystal structure; iron binding motif; isopenicillin N synthase; mechanism of action;
D O I
10.1023/A:1001723202234
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Isopenicillin N synthase is a key enzyme in the biosynthesis of penicillin and cephalosporin antibiotics, catalyzing the oxidative ring closure of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine to form isopenicillin N. Recent advances in our understanding of the unique chemistry of this enzyme have come through the combined application of spectroscopic, molecular genetic and crystallographic approaches and led to important new insights into the structure and function of this enzyme. Here we review new information on the nature of the endogenous ligands that constitute the ferrous iron active site, sequence evidence for a novel structural motif involved in iron binding in this and related non-heme iron dependent dioxygenases, crystal structure studies on the enzyme and its substrate complex and the impact of these and site-directed mutagenesis studies for unraveling the mechanism of the isopenicillin N synthase reaction.
引用
收藏
页码:33 / 39
页数:7
相关论文
共 25 条
  • [1] PENICILLIN AND CEPHALOSPORIN BIOSYNTHETIC GENES - STRUCTURE, ORGANIZATION, REGULATION, AND EVOLUTION
    AHARONOWITZ, Y
    COHEN, G
    MARTIN, JF
    [J]. ANNUAL REVIEW OF MICROBIOLOGY, 1992, 46 : 461 - 495
  • [2] THE BIOSYNTHESIS OF PENICILLINS AND CEPHALOSPORINS
    BALDWIN, JE
    ABRAHAM, E
    [J]. NATURAL PRODUCT REPORTS, 1988, 5 (02) : 129 - 145
  • [3] ISOPENICILLIN-N SYNTHASE - MECHANISTIC STUDIES
    BALDWIN, JE
    BRADLEY, M
    [J]. CHEMICAL REVIEWS, 1990, 90 (07) : 1079 - 1088
  • [4] A HEURISTIC APPROACH TO THE ANALYSIS OF ENZYMATIC CATALYSIS - REACTION OF DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-D-ALPHA-AMINOBUTYRATE AND DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-D-ALLYLGLYCINE CATALYZED BY ISOPENICILLIN-N SYNTHASE ISOZYMES
    BLACKBURN, JM
    SUTHERLAND, JD
    BALDWIN, JE
    [J]. BIOCHEMISTRY, 1995, 34 (22) : 7548 - 7562
  • [5] Ferrous active site of isopenicillin N synthase: Genetic and sequence analysis of the endogenous ligands
    Borovok, I
    Landman, O
    KreisbergZakarin, R
    Aharonowitz, Y
    Cohen, G
    [J]. BIOCHEMISTRY, 1996, 35 (06) : 1981 - 1987
  • [6] COHEN G, 1995, SYMP SOC GEN MICROBI, V53, P139
  • [7] MICROBIAL ISOPENICILLIN-N SYNTHASE GENES - STRUCTURE, FUNCTION, DIVERSITY AND EVOLUTION
    COHEN, G
    SHIFFMAN, D
    MEVARECH, M
    AHARONOWITZ, Y
    [J]. TRENDS IN BIOTECHNOLOGY, 1990, 8 (04) : 105 - 111
  • [8] Cooper R D, 1993, Bioorg Med Chem, V1, P1, DOI 10.1016/S0968-0896(00)82098-2
  • [9] REACTIONS OF NONHEME IRON(II) CENTERS WITH DIOXYGEN IN BIOLOGY AND CHEMISTRY
    FEIG, AL
    LIPPARD, SJ
    [J]. CHEMICAL REVIEWS, 1994, 94 (03) : 759 - 805
  • [10] CRYSTALLIZATION AND PRELIMINARY-X-RAY DIFFRACTION STUDIES ON A RECOMBINANT ISOPENICILLIN N-SYNTHASE FROM CEPHALOSPORIUM-ACREMONIUM
    FUJISHIMA, Y
    NORDLUND, P
    PELOSI, G
    SCHOFIELD, CJ
    COLE, SCJ
    BALDWIN, JE
    HAJDU, J
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1994, 242 (05) : 712 - 714