Bhatnagar R S, Fütterer K, Farazi T A, Korolev S, Murray C L, Jackson-Machelski E, Gokel G W, Gordon J I, Waksman G
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nat Struct Biol. 1998 Dec;5(12):1091-7. doi: 10.1038/4202.
N-myristoyltransferase (Nmt) attaches myristate to the N-terminal glycine of many important eukaryotic and viral proteins. It is a target for anti-fungal and anti-viral therapy. We have determined the structure, to 2.9 A resolution, of a ternary complex of Saccharomyces cerevisiae Nmt1p with bound myristoylCoA and peptide substrate analogs. The model reveals structural features that define the enzyme's substrate specificities and regulate the ordered binding and release of substrates and products. A novel catalytic mechanism is proposed involving deprotonation of the N-terminal ammonium of a peptide substrate by the enzyme's C-terminal backbone carboxylate.
N-肉豆蔻酰基转移酶（Nmt）将肉豆蔻酸连接到许多重要的真核生物和病毒蛋白的N端甘氨酸上。它是抗真菌和抗病毒治疗的靶点。我们已经确定了酿酒酵母Nmt1p与结合的肉豆蔻酰辅酶A和肽底物类似物的三元复合物的结构，分辨率为2.9埃。该模型揭示了定义酶底物特异性并调节底物和产物有序结合与释放的结构特征。提出了一种新的催化机制，涉及酶的C端主链羧酸盐使肽底物的N端铵去质子化。
