Structure and implications for the thermal stability of phosphopantetheine adenylyltransferase from Thermus thermophilus

Hitomi Takahashi, Eiji Inagaki, Yayoi Fujimoto, Chizu Kuroishi, Yuichi Nodake, Yuki Nakamura, Fumio Arisaka, Katsuhide Yutani, Seiki Kuramitsu, Shigeyuki Yokoyama, Masaki Yamamoto, Masashi Miyano, Tahir H. Tahirov

Research output: Contribution to journalArticle

26 Scopus citations


Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in bacteria that catalyzes the rate-limiting step in coenzyme A (CoA) biosynthesis by transferring an adenylyl group from ATP to 4′-phosphopantetheine (Ppant), yielding 3′-dephospho-CoA (dPCoA). The crystal structure of PPAT from Thermus thermophilus HB8 (Tt PPAT) complexed with Ppant has been determined by the molecular-replacement method at 1.5 Å resolution. The overall fold of the enzyme is almost the same as that of Escherichia coli PPAT, a hexamer having point group 32. The asymmetric unit of Tt PPAT contains a monomer and the crystallographic triad and dyad coincide with the threefold and twofold axes of the hexamer, respectively. Most of the important atoms surrounding the active site in E. coli PPAT are conserved in Tt PPAT, indicating similarities in their substrate binding and enzymatic reaction. The notable difference between E. coli PPAT and Tt PPAT is the simultaneous substrate recognition by all six subunits of Tt PPAT compared with substrate recognition by only three subunits in E. coli PPAT. Comparative analysis also revealed that the higher stability of Tt PPAT arises from stabilization of each subunit by hydrophobic effects, hydrogen bonds and entropic effects.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalActa Crystallographica Section D: Biological Crystallography
Issue number1
Publication statusPublished - Jan 1 2004


ASJC Scopus subject areas

  • Structural Biology

Cite this