Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase from Staphylococcus aureus

被引：83

作者：

Hennig, M ^{[1
]}

D'Arcy, A ^{[1
]}

Hampele, IC ^{[1
]}

Page, MGP ^{[1
]}

Oefner, C ^{[1
]}

Dale, GE ^{[1
]}

机构：

[1] Hoffmann La Roche Ag, Preclin Res, CH-4070 Basel, Switzerland

来源：

NATURE STRUCTURAL BIOLOGY | 1998年 / 5卷 / 05期

关键词：

D O I：

10.1038/nsb0598-357

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：

Dihydroneopterin aldolase catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin during the de novo synthesis of folic acid from guanosine triphosphate. The gene encoding the dihydroneopterin aldolase from S. aureus has been cloned, sequenced and expressed in Escherichia coli. The protein has been purified for biochemical characterization and its X-ray structure determined at 1.65 Angstrom resolution. The protein forms an octamer of 110,000 M-r molecular weight. Four molecules assemble into a ring, and two rings come together to give a cylinder with a hole of at least 13 Angstrom diameter. The structure of the binary complex with the product 6-hydroxymethyl-7,8-dihydropterin has defined the location of the active site. The structural information and results of site directed mutagenesis allow an enzyme reaction mechanism to be proposed.

引用

页码：357 / 362

页数：6

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