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Crystal structure of phosphopantothenate synthetase from Thermococcus kodakarensis
Author(s) -
Kishimoto Asako,
Kita Akiko,
Ishibashi Takuya,
Tomita Hiroya,
Yokooji Yuusuke,
Imanaka Tadayuki,
Atomi Haruyuki,
Miki Kunio
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24546
Subject(s) - archaea , thermococcus , enzyme , adenylate kinase , dimer , pyrococcus horikoshii , biochemistry , chemistry , euryarchaeota , stereochemistry , mutagenesis , bacteria , transferase , cofactor , biology , crystallography , gene , genetics , mutation , organic chemistry
Bacteria/eukaryotes share a common pathway for coenzyme A biosynthesis which involves two enzymes to convert pantoate to 4′‐phosphopantothenate. These two enzymes are absent in almost all archaea. Recently, it was reported that two novel enzymes, pantoate kinase, and phosphopantothenate synthetase (PPS), are responsible for this conversion in archaea. Here, we report the crystal structure of PPS from the hyperthermophilic archaeon, Thermococcus kodakarensis and its complexes with substrates, ATP, and ATP and 4‐phosphopantoate. PPS forms an asymmetric homodimer, in which two monomers composing a dimer, deviated from the exact twofold symmetry, displaying 4°–13° distortion. The structural features are consistent with the mutagenesis data and the results of biochemical experiments previously reported. Based on these structures, we discuss the catalytic mechanism by which PPS produces phosphopantoyl adenylate, which is thought to be a reaction intermediate. Proteins 2014; 82:1924–1936. © 2014 Wiley Periodicals, Inc.