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Research Article

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Mol. Cells 2011; 32(5): 431-435

Published online September 9, 2011

https://doi.org/10.1007/s10059-011-0102-y

© The Korean Society for Molecular and Cellular Biology

Crystal Structure of Phosphopantetheine Adenylyltransferase from Enterococcus faecalis in the Ligand-Unbound State and in Complex with ATP and Pantetheine

Hye-Jin Yoon1, Ji Yong Kang1, Bunzo Mikami2, Hyung Ho Lee3,4,*, and Se Won Suh1,5,*

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1Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea, 2Laboratory of Quality Design and Exploitation, Division of Agronomy and Horticultural Science, Graduate School of Agriculture, Kyoto University, Kyoto 611-0011, Japan, 3Department of Bio and Nano Chemistry, Kookmin University, Seoul 136-702, Korea, 4Department of Integrative Biomedical Science and Engineering, Kookmin University, Seoul 136-702, Korea, 5Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea

Correspondence to : *Correspondence: sewonsuh@snu.ac.kr (SWS); hhlee@kookmin.ac.kr (HHL)

Received: May 11, 2011; Revised: August 21, 2011; Accepted: August 23, 2011

Abstract

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Phosphopantetheine adenylyltransferase (PPAT) catalyzes the reversible transfer of an adenylyl group from ATP to 4?-phosphopantetheine (Ppant) to form dephospho-CoA (dPCoA) and pyrophosphate in the Coenzyme A (CoA) biosynthetic pathway. Importantly, PPATs are a potential target for developing antibiotics because bacterial and mammalian PPATs share little sequence homology. Previ-ous structural studies revealed the mechanism of the recognizing substrates and products. The binding modes of ATP, ADP, Ppant, and dPCoA are highly similar in all known structures, whereas the binding modes of CoA or 3?-phosphoadenosine 5?-phosphosulfate binding are novel. To provide further structural information on ligand binding by PPATs, the crystal structure of PPAT from Enterococ-cus faecalis was solved in three forms: (i) apo form, (ii) binary complex with ATP, and (iii) binary complex with pantetheine. The substrate analog, pantetheine, binds to the active site in a similar manner to Ppant. The new struc-tural information reported in this study including pant-etheine as a potent inhibitor of PPAT will supplement the existing structural data and should be useful for structure-based antibacterial discovery against PPATs.

Keywords coenzyme A biosynthetic pathway, Enterococcus faecalis, pantetheine, phosphopantetheine adenylyltransferase, PPAT

Article

Research Article

Mol. Cells 2011; 32(5): 431-435

Published online November 30, 2011 https://doi.org/10.1007/s10059-011-0102-y

Copyright © The Korean Society for Molecular and Cellular Biology.

Crystal Structure of Phosphopantetheine Adenylyltransferase from Enterococcus faecalis in the Ligand-Unbound State and in Complex with ATP and Pantetheine

Hye-Jin Yoon1, Ji Yong Kang1, Bunzo Mikami2, Hyung Ho Lee3,4,*, and Se Won Suh1,5,*

1Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea, 2Laboratory of Quality Design and Exploitation, Division of Agronomy and Horticultural Science, Graduate School of Agriculture, Kyoto University, Kyoto 611-0011, Japan, 3Department of Bio and Nano Chemistry, Kookmin University, Seoul 136-702, Korea, 4Department of Integrative Biomedical Science and Engineering, Kookmin University, Seoul 136-702, Korea, 5Department of Biophysics and Chemical Biology, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea

Correspondence to:*Correspondence: sewonsuh@snu.ac.kr (SWS); hhlee@kookmin.ac.kr (HHL)

Received: May 11, 2011; Revised: August 21, 2011; Accepted: August 23, 2011

Abstract

Phosphopantetheine adenylyltransferase (PPAT) catalyzes the reversible transfer of an adenylyl group from ATP to 4?-phosphopantetheine (Ppant) to form dephospho-CoA (dPCoA) and pyrophosphate in the Coenzyme A (CoA) biosynthetic pathway. Importantly, PPATs are a potential target for developing antibiotics because bacterial and mammalian PPATs share little sequence homology. Previ-ous structural studies revealed the mechanism of the recognizing substrates and products. The binding modes of ATP, ADP, Ppant, and dPCoA are highly similar in all known structures, whereas the binding modes of CoA or 3?-phosphoadenosine 5?-phosphosulfate binding are novel. To provide further structural information on ligand binding by PPATs, the crystal structure of PPAT from Enterococ-cus faecalis was solved in three forms: (i) apo form, (ii) binary complex with ATP, and (iii) binary complex with pantetheine. The substrate analog, pantetheine, binds to the active site in a similar manner to Ppant. The new struc-tural information reported in this study including pant-etheine as a potent inhibitor of PPAT will supplement the existing structural data and should be useful for structure-based antibacterial discovery against PPATs.

Keywords: coenzyme A biosynthetic pathway, Enterococcus faecalis, pantetheine, phosphopantetheine adenylyltransferase, PPAT

Mol. Cells
Jun 30, 2023 Vol.46 No.6, pp. 329~398
COVER PICTURE
The cellular proteostasis network is adaptively modulated upon cellular stress, thereby protecting cells from proteostasis collapse. Heat shock induces the translocation of misfolded proteins and the chaperone protein HSP70 into nucleolus, where nuclear protein quality control primarily occurs. Nuclear RNA export factor 1 (green), nucleolar protein fibrillarin (red), and nuclei (blue) were visualized in NIH3T3 cells under basal (left) and heat shock (right) conditions (Park et al., pp. 374-386).
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