Morris Van K, Izard Tina
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis TN 38105, USA.
Protein Sci. 2004 Sep;13(9):2547-52. doi: 10.1110/ps.04816904.
Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in prokaryotic coenzyme A (CoA) biosynthesis, directing the transfer of an adenylyl group from ATP to 4'-phosphopantetheine (Ppant) to yield dephospho-CoA (dPCoA). The crystal structures of Escherichia coli PPAT bound to its substrates, product, and inhibitor revealed an allosteric hexameric enzyme with half-of-sites reactivity, and established an in-line displacement catalytic mechanism. To provide insight into the mechanism of ligand binding we solved the apoenzyme (Apo) crystal structure of PPAT from Mycobacterium tuberculosis. In its Apo form, PPAT is a symmetric hexamer with an open solvent channel. However, ligand binding provokes asymmetry and alters the structure of the solvent channel, so that ligand binding becomes restricted to one trimer.
磷酸泛酰巯基乙胺腺苷酰转移酶（PPAT）催化原核生物辅酶A（CoA）生物合成的倒数第二步反应，即将腺苷酰基从ATP转移至4'-磷酸泛酰巯基乙胺（Ppant），生成脱磷酸辅酶A（dPCoA）。大肠杆菌PPAT与其底物、产物及抑制剂结合的晶体结构显示，该酶是一种具有半位点反应性的变构六聚体酶，并确立了一种线性位移催化机制。为深入了解配体结合机制，我们解析了结核分枝杆菌PPAT的无配体酶（Apo）晶体结构。处于Apo形式时，PPAT是一种具有开放溶剂通道的对称六聚体。然而，配体结合会引发不对称性并改变溶剂通道的结构，从而使配体结合局限于一个三聚体。
