The structure and function of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Haemophilus influenzae

被引：51

作者：

Hennig, M ^{[1
]}

Dale, GE ^{[1
]}

D'Arcy, A ^{[1
]}

Danel, F ^{[1
]}

Fischer, S ^{[1
]}

Gray, CP ^{[1
]}

Jolidon, S ^{[1
]}

Müller, F ^{[1
]}

Page, MGP ^{[1
]}

Pattison, P ^{[1
]}

Oefner, C ^{[1
]}

机构：

[1] F Hoffmann La Roche & Co Ltd, Pharma Preclin Res, CH-4070 Basel, Switzerland

来源：

JOURNAL OF MOLECULAR BIOLOGY | 1999年 / 287卷 / 02期

关键词：

HPPK; pterin; pyrophosphokinase; MAD; X-ray structure;

D O I：

10.1006/jmbi.1999.2623

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 gene encoding the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase of Haemophilus influenzae has been cloned and expressed in Escherichia coli. A complex of the purified protein with a substrate analog has been crystallized and its structure solved by multiple anomalous dispersion using phase information obtained from a single crystal of selenomethione-labeled protein. The enzyme folds into a four-stranded antiparallel beta-sheet flanked on one side by two alpha-helices and on the other by three consecutive alpha-helices, giving a novel beta(1)alpha(1)beta(2)beta(3)alpha(2)beta(4)alpha(3)alpha(4)alpha(5) polypeptide topology. The three-dimensional structure of a binary complex has been refined at 2.1 Angstrom resolution. The location of the substrate analog and a sulfate ion gives important insight into the molecular mechanism of the enzyme. (C) 1999 Academic Press.

引用

页码：211 / 219

页数：9

共 45 条

[21] USE OF NONLINEAR-REGRESSION TO ANALYZE ENZYME KINETIC DATA - APPLICATION TO SITUATIONS OF SUBSTRATE CONTAMINATION AND BACKGROUND SUBTRACTION [J].

LEATHERBARROW, RJ .

ANALYTICAL BIOCHEMISTRY, 1990, 184 (02) :274-278

[22] DNA-SEQUENCE OF FOLATE BIOSYNTHESIS GENE-SULD, ENCODING HYDROXYMETHYLDIHYDROPTERIN PYROPHOSPHOKINASE IN STREPTOCOCCUS-PNEUMONIAE, AND CHARACTERIZATION OF THE ENZYME [J].

LOPEZ, P ;

GREENBERG, B ;

LACKS, SA .

JOURNAL OF BACTERIOLOGY, 1990, 172 (09) :4766-4774

[23] Raster3D: Photorealistic molecular graphics [J].

Merritt, EA ;

Bacon, DJ .

MACROMOLECULAR CRYSTALLOGRAPHY, PT B, 1997, 277 :505-524

[24]

MITSUDA H, 1970, 4 INT S PTER, P295

[25] MUTATIONS AT POSITION-153 AND POSITION-328 IN ESCHERICHIA-COLI ALKALINE-PHOSPHATASE PROVIDE INSIGHT TOWARDS THE STRUCTURE AND FUNCTION OF MAMMALIAN AND YEAST ALKALINE-PHOSPHATASES [J].

MURPHY, JE ;

TIBBITTS, TT ;

KANTROWITZ, ER .

JOURNAL OF MOLECULAR BIOLOGY, 1995, 253 (04) :604-617

[26]

Nicholls A., 1992, GRASP GRAPHICAL REPR

[27]

OTWINOWSKI Z, 1993, P CCP4 STUD WEEK DAT, P56

[28] Isolation and molecular characterization of the bifunctional hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase gene from Toxoplasma gondii [J].

Pashley, TV ;

Volpe, F ;

Pudney, M ;

Hyde, JE ;

Sims, PFG ;

Delves, CJ .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1997, 86 (01) :37-47

[29] 3-DIMENSIONAL CRYSTAL-STRUCTURES OF ESCHERICHIA-COLI MET REPRESSOR WITH AND WITHOUT COREPRESSOR [J].

RAFFERTY, JB ;

SOMERS, WS ;

STGIRONS, I ;

PHILLIPS, SEV .

NATURE, 1989, 341 (6244) :705-710

[30] Folate biosynthesis in higher plants: Purification and molecular cloning of a bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase localized in mitochondria [J].

Rebeille, F ;

Macherel, D ;

Mouillon, JM ;

Garin, J ;

Douce, R .

EMBO JOURNAL, 1997, 16 (05) :947-957

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