Lee Hyung Ho, Yoon Hye Jin, Kang Ji Yong, Park Ji Hyeon, Kim Do Jin, Choi Kwang Hyun, Lee Seung Kyu, Song Jinsu, Kim Hie Joon, Suh Se Won
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Oct 1;65(Pt 10):987-91. doi: 10.1107/S1744309109036616. Epub 2009 Sep 23.
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.
细菌磷酸泛酰巯基乙胺腺苷酰转移酶（PPAT）催化辅酶A（CoA）生物合成途径中的倒数第二步反应。它催化腺苷酰基从ATP可逆地转移至4'-磷酸泛酰巯基乙胺（Ppant），形成脱磷酸辅酶A（dPCoA）和焦磷酸。先前的结构研究已揭示了细菌PPAT如何识别几种配体。ATP、ADP、Ppant和dPCoA以高度相似的方式结合到同一结合位点，而CoA则以不同模式结合到部分重叠的位点。为了提供关于配体结合的更多结构见解，金黄色葡萄球菌PPAT与3'-磷酸腺苷5'-磷酸硫酸酯（PAPS）形成的二元复合物的晶体结构得以解析。这项研究意外地揭示了一种配体与PPAT结合的新模式，从而为基于结构发现细菌PPAT抑制剂提供了潜在有用的信息。
