Edwards Thomas E, Gardberg Anna S, Phan Isabelle Q H, Zhang Yang, Staker Bart L, Myler Peter J, Lorimer Donald D
Seattle Structural Genomics Center for Infectious Disease, USA.
Acta Crystallogr F Struct Biol Commun. 2015 May;71(Pt 5):560-5. doi: 10.1107/S2053230X1500179X. Epub 2015 Apr 21.
Uridine diphosphate N-acetylglucosamine pyrophosphorylase (UAP) catalyzes the final step in the synthesis of UDP-GlcNAc, which is involved in cell-wall biogenesis in plants and fungi and in protein glycosylation. Small-molecule inhibitors have been developed against UAP from Trypanosoma brucei that target an allosteric pocket to provide selectivity over the human enzyme. A 1.8 Å resolution crystal structure was determined of UAP from Entamoeba histolytica, an anaerobic parasitic protozoan that causes amoebic dysentery. Although E. histolytica UAP exhibits the same three-domain global architecture as other UAPs, it appears to lack three α-helices at the N-terminus and contains two amino acids in the allosteric pocket that make it appear more like the enzyme from the human host than that from the other parasite T. brucei. Thus, allosteric inhibitors of T. brucei UAP are unlikely to target Entamoeba UAPs.
尿苷二磷酸N - 乙酰葡糖胺焦磷酸化酶（UAP）催化UDP - GlcNAc合成的最后一步，UDP - GlcNAc参与植物和真菌的细胞壁生物合成以及蛋白质糖基化。已经开发出针对布氏锥虫UAP的小分子抑制剂，这些抑制剂靶向变构口袋以提供对人源酶的选择性。确定了溶组织内阿米巴UAP的分辨率为1.8 Å的晶体结构，溶组织内阿米巴是一种导致阿米巴痢疾的厌氧寄生原生动物。尽管溶组织内阿米巴UAP与其他UAP具有相同的三结构域整体结构，但它在N端似乎缺少三个α螺旋，并且在变构口袋中含有两个氨基酸，这使得它看起来更像人源宿主的酶，而不是来自另一种寄生虫布氏锥虫的酶。因此，布氏锥虫UAP的变构抑制剂不太可能靶向溶组织内阿米巴UAP。
