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.
Lee
Hyung Ho
HH
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Yoon
Hye Jin
HJ
Kang
Ji Yong
JY
Park
Ji Hyeon
JH
Kim
Do Jin
DJ
Choi
Kwang Hyun
KH
Lee
Seung Kyu
SK
Song
Jinsu
J
Kim
Hie Joon
HJ
Suh
Se Won
SW
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