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Crystal Structure of the Hyperthermophilic Inorganic Pyrophosphatase from the Archaeon Pyrococcus horikoshii

Binbin Liu ^* , Mark Bartlam ^* , Renjun Gao , Weihong Zhou ^*, Hai Pang ^*, Yiwei Liu ^*, Yan Feng  and Zihe Rao ^* 

^* Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023, China; and National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China

Correspondence: Address reprint requests to Zihe Rao, Laboratory of Structural Biology, Dept. of Biological Science and Biotechnology, Tsinghua University, Beijing 100084, P. R. China. Tel.: 86-10-6277-1493; Fax: 86-10-6277-3145; E-mail: raozh{at}xtal.tsinghua.edu.cn.

A homolog to the eubacteria inorganic pyrophosphatase (PPase, EC 3.6.1.1) was found in the genome of the hyperthermophilic archaeon Pyrococcus horikoshii. This inorganic pyrophosphatase (Pho-PPase) grows optimally at 88°C. To understand the structural basis for the thermostability of Pho-PPase, we have determined the crystal structure to 2.66 Å resolution. The crystallographic asymmetric unit contains three monomers related by approximate threefold symmetry, and a hexamer is built up by twofold crystallographic symmetry. The main-chain fold of Pho-PPase is almost identical to that of the known crystal structure of the model from Sulfolobus acidocaldarius. A detailed comparison of the crystal structure of Pho-PPase with related structures from S. acidocaldarius, Thermus thermophilus, and Escherichia coli shows significant differences that may account for the difference in their thermostabilities. A reduction in thermolabile residues, additional aromatic residues, and more intimate association between subunits all contribute to the larger thermophilicity of Pho-PPase. In particular, deletions in two loops surrounding the active site help to stabilize its conformation, while ion-pair networks unique to Pho-PPase are located in the active site and near the C-terminus. The identification of structural features that make PPases more adaptable to extreme temperature should prove helpful for future biotechnology applications.

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