MUTAGENESIS STUDIES ON THE AMINO-ACID-RESIDUES INVOLVED IN THE IRON-BINDING AND THE ACTIVITY OF HUMAN 5-LIPOXYGENASE

被引：30

作者：

ISHII, S

NOGUCHI, M

MIYANO, M

MATSUMOTO, T

NOMA, M

机构：

[1] Life Science Research Laboratory, Japan Tobacco Inc., Midori-ku, Yokohama, Kanagawa, 227

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1992年 / 182卷 / 03期

关键词：

D O I：

10.1016/0006-291X(92)91901-2

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：

Human 5-lipoxygenase contains a non-heme iron essential for its activity. In order to determine which amino acid residues are involved in the iron-binding and the lipoxygenase activity, nine amino acid residues in highly homologous regions among the lipoxygenases were individually replaced by means of site-directed mutagenesis. Mutant 5-lipoxygenases in which His-367 or His-550 was replaced by either Asn or Ala, His-372 by either Asn or Ser, or Glu-376 by Gln were completely devoid of the activity. Though mutants containing an alanine residue instead of His-390 or His-399 lacked the activity, the corresponding asparagine substituted mutants exhibited. The other mutants retained the enzyme activity. These results strongly suggest that His-367, His-372, His-550 and Glu-376 are crucial for 5-lipoxygenase activity and coordinate to the essential iron. © 1992.

引用

收藏

页码：1482 / 1490

页数：9

相关论文

共 31 条

[1] STRUCTURE OF HUMAN LACTOFERRIN AT 3.2-A RESOLUTION [J].

ANDERSON, BF ;

BAKER, HM ;

DODSON, EJ ;

NORRIS, GE ;

RUMBALL, SV ;

WATERS, JM ;

BAKER, EN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (07) :1769-1773

[2] MOLECULAR-STRUCTURE OF SERUM TRANSFERRIN AT 3.3-A RESOLUTION [J].

BAILEY, S ;

EVANS, RW ;

GARRATT, RC ;

GORINSKY, B ;

HASNAIN, S ;

HORSBURGH, C ;

JHOTI, H ;

LINDLEY, PF ;

MYDIN, A ;

SARRA, R ;

WATSON, JL .

BIOCHEMISTRY, 1988, 27 (15) :5804-5812

[3]

BALCAREK JM, 1988, J BIOL CHEM, V263, P13937

[4] DEMONSTRATION BY EPR SPECTROSCOPY OF FUNCTIONAL ROLE OF IRON IN SOYBEAN LIPOXYGENASE-1 [J].

DEGROOT, JJM ;

VELDINK, GA ;

VLIEGENTHART, JFG ;

BOLDINGH, J ;

WEVER, R ;

VANGELDER, BF .

BIOCHIMICA ET BIOPHYSICA ACTA, 1975, 377 (01) :71-79

[5] THE INITIAL CHARACTERIZATION OF THE IRON ENVIRONMENT IN LIPOXYGENASE BY MOSSBAUER-SPECTROSCOPY [J].

DUNHAM, WR ;

CARROLL, RT ;

THOMPSON, JF ;

SANDS, RH ;

FUNK, MO .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1990, 190 (03) :611-617

[6] THE CDNA CLONING OF A PEA (PISUM-SATIVUM) SEED LIPOXYGENASE - SEQUENCE COMPARISONS OF THE 2 MAJOR PEA SEED LIPOXYGENASE ISOFORMS [J].

EALING, PM ;

CASEY, R .

BIOCHEMICAL JOURNAL, 1989, 264 (03) :929-932

[7] THE COMPLETE SEQUENCE OF THE RABBIT ERYTHROID CELL-SPECIFIC 15-LIPOXYGENASE MESSENGER-RNA - COMPARISON OF THE PREDICTED AMINO-ACID SEQUENCE OF THE ERYTHROCYTE LIPOXYGENASE WITH OTHER LIPOXYGENASES [J].

FLEMING, J ;

THIELE, BJ ;

CHESTER, J ;

OPREY, J ;

JANETZKI, S ;

AITKEN, A ;

ANTON, IA ;

RAPOPORT, SM ;

HARRISON, PR .

GENE, 1989, 79 (01) :181-188

[8] NATIVE AND MUTANT 5-LIPOXYGENASE EXPRESSION IN A BACULOVIRUS INSECT CELL SYSTEM [J].

FUNK, CD ;

GUNNE, H ;

STEINER, H ;

IZUMI, T ;

SAMUELSSON, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (08) :2592-2596

[9] MOLECULAR-CLONING, PRIMARY STRUCTURE, AND EXPRESSION OF THE HUMAN PLATELET ERYTHROLEUKEMIA CELL 12-LIPOXYGENASE [J].

FUNK, CD ;

FURCI, L ;

FITZGERALD, GA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (15) :5638-5642

[10] SOLVING THE STRUCTURE OF HUMAN H-FERRITIN BY GENETICALLY ENGINEERING INTERMOLECULAR CRYSTAL CONTACTS [J].

LAWSON, DM ;

ARTYMIUK, PJ ;

YEWDALL, SJ ;

SMITH, JMA ;

LIVINGSTONE, JC ;

TREFFRY, A ;

LUZZAGO, A ;

LEVI, S ;

AROSIO, P ;

CESARENI, G ;

THOMAS, CD ;

SHAW, WV ;

HARRISON, PM .

NATURE, 1991, 349 (6309) :541-544

← 1 2 3 4 →