Dimeric dUTPases, HisE, and MazG belong to a new superfamily of all-α NTP pyrophosphohydrolases with potential "house-cleaning" functions

被引：78

作者：

Moroz, OV

Murzin, AG ^{[1
]}

Makarova, KS

Koonin, EV

Wilson, KS

Galperin, MY

机构：

[1] Univ York, Dept Chem, York Struct Biol Lab, York YO10 5YW, N Yorkshire, England

[2] MRC, Ctr Prot Engn, Cambridge CB2 2QH, England

[3] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2005年 / 347卷 / 02期

关键词：

histidine biosynthesis; non-canonical nucleotides; mutagenesis; gene silencing; oxidative damage;

D O I：

10.1016/j.jmb.2005.01.030

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：

Structure-guided analysis of the new dimeric dUTPase family revealed its sequence relationship to the phage T4 dCTPase, phosphoribosyl-ATP pyrophosphatase HisE, NTP pyrophosphatase MazG, and several uncharacterized protein families, including the human protein XTP3TPA (RS21-C6), which is overexpressed in embryonic and cancer cells. Comparison with the recently determined structure of a MazG-like protein from Sulfolobus solfataricus supported the unification of these enzymes in one superfamily of all-alpha NTP pyrophosphatases, suggesting that dimeric dUTPases evolved from a tetrameric MazG-like ancestor by gene duplication. Analysis of the structure of the Sulfolobus MazG points to 2-hydroxyadenosine (isoguanosine) triphosphate, a product of oxidative damage of ATP, as the most likely substrate. We predict that uncharacterized members of this superfamily perform "house-cleaning" functions by hydrolyzing abnormal NTPs and are functionally analogous to the structurally unrelated hydrolases of the Nudix superfamily. We outline probable tertiary and quaternary structures of the all-alpha NTP pyrophosphatase superfamily members. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：243 / 255

页数：13

共 72 条

[21] Isolation and characterization of a histidine biosynthetic gene in Arabidopsis encoding a polypeptide with two separate domains for phosphoribosyl-ATP pyrophosphohydrolase and phosphoribosyl-AMP cyclohydrolase [J].