The structure of Staphylococcus aureus phosphopantetheine adenylyltransferase in complex with 3'-phosphoadenosine 5'-phosphosulfate reveals a new ligand-binding mode.
Bacterial phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway. It catalyzes the reversible transfer of an adenylyl group from ATP to 4'-phosphopantetheine (Ppant) to form dephospho-CoA (dPCoA) and pyrophosphate. Previous structural studies have revealed how several ligands are recognized by bacterial PPATs. ATP, ADP, Ppant and dPCoA bind to the same binding site in a highly similar manner, while CoA binds to a partially overlapping site in a different mode. To provide further structural insights into ligand binding, the crystal structure of Staphylococcus aureus PPAT was solved in a binary complex with 3'-phosphoadenosine 5'-phosphosulfate (PAPS). This study unexpectedly revealed a new mode of ligand binding to PPAT, thus providing potentially useful information for structure-based discovery of inhibitors of bacterial PPATs.
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Hyung Ho
HH
Lee
Hye Jin
HJ
Yoon
Ji Yong
JY
Kang
Ji Hyeon
JH
Park
Do Jin
DJ
Kim
Kwang Hyun
KH
Choi
Seung Kyu
SK
Lee
Jinsu
J
Song
Hie Joon
HJ
Kim
Se Won
SW
Suh
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000378:metabolism; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000201:enzymology
D010724:Phosphoadenosine Phosphosulfate; D009713:Nucleotidyltransferases; C022315:pantetheine-phosphate adenylyltransferase