Edwards Thomas E, Leibly David J, Bhandari Janhavi, Statnekov Jacob B, Phan Isabelle, Dieterich Shellie H, Abendroth Jan, Staker Bart L, Van Voorhis Wesley C, Myler Peter J, Stewart Lance J
Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt 9):1032-7. doi: 10.1107/S1744309111004349. Epub 2011 Aug 13.
Phosphopantetheine adenylyltransferase (PPAT) catalyzes the fourth of five steps in the coenzyme A biosynthetic pathway, reversibly transferring an adenylyl group from ATP onto 4'-phosphopantetheine to yield dephospho-coenzyme A and pyrophosphate. Burkholderia pseudomallei is a soil- and water-borne pathogenic bacterium and the etiologic agent of melioidosis, a potentially fatal systemic disease present in southeast Asia. Two crystal structures are presented of the PPAT from B. pseudomallei with the expectation that, because of the importance of the enzyme in coenzyme A biosynthesis, they will aid in the search for defenses against this pathogen. A crystal grown in ammonium sulfate yielded a 2.1 Å resolution structure that contained dephospho-coenzyme A with partial occupancy. The overall structure and ligand-binding interactions are quite similar to other bacterial PPAT crystal structures. A crystal grown at low pH in the presence of coenzyme A yielded a 1.6 Å resolution structure in the same crystal form. However, the experimental electron density was not reflective of fully ordered coenzyme A, but rather was only reflective of an ordered 4'-diphosphopantetheine moiety.
磷酸泛酰巯基乙胺腺苷酰转移酶（PPAT）催化辅酶A生物合成途径五步中的第四步，可逆地将腺苷酰基从ATP转移到4'-磷酸泛酰巯基乙胺上，生成脱磷酸辅酶A和焦磷酸。伯克霍尔德菌是一种土壤和水源性病原菌，也是类鼻疽病的病原体，类鼻疽病是一种在东南亚存在的潜在致命性全身性疾病。本文给出了伯克霍尔德菌PPAT的两种晶体结构，预期由于该酶在辅酶A生物合成中的重要性，它们将有助于寻找针对这种病原体的防御方法。在硫酸铵中生长的晶体产生了一个分辨率为2.1 Å的结构，其中含有部分占据的脱磷酸辅酶A。其整体结构和配体结合相互作用与其他细菌PPAT晶体结构非常相似。在低pH值且存在辅酶A的条件下生长的晶体产生了一个分辨率为1.6 Å的相同晶型结构。然而，实验电子密度并非完全有序的辅酶A的反映，而仅反映了有序的4'-二磷酸泛酰巯基乙胺部分。
