Ojuromi Oladele T, Giwa Abdulazeez O, Gardberg Anna, Subramanian Sandhya, Myler Peter J, Abendroth Jan, Staker Bart, Asojo Oluwatoyin A
Zoology and Environmental Biology, Lagos State University, Nigeria.
Freelance Structural Biology Consultant, Greater Boston Area, Massachusetts, USA.
Acta Crystallogr F Struct Biol Commun. 2025 Jun 1;81(Pt 6):226-234. doi: 10.1107/S2053230X25003875. Epub 2025 May 2.
Entamoeba histolytica causes amebiasis, a neglected disease that kills ∼100 000 people globally each year. Due to emerging drug resistance, E. histolytica is one of the target organisms for structure-based drug discovery by the Seattle Structural Genomics Center for Infectious Disease (SSGCID). Purification, crystallization and three structures of the putative drug target endoribonuclease L-PSP from E. histolytica (EhL-PSP) are presented. EhL-PSP has a two-layer α/β-sandwich with structural homology to endoribonuclease L-PSP. All three structures reveal the prototypical YjgF/YER057c/UK114 family trimer topology with accessible allosteric active sites. Citrate molecules from the crystallization solution are bound to the allosteric site in two of the three reported structures. The large allosteric site of EhL-PSP is well conserved with bacterial YjgF/YER057c/UK114 family members and could be targeted for inhibition, drug discovery or repurposing.
溶组织内阿米巴可引发阿米巴病，这是一种被忽视的疾病，每年在全球导致约10万人死亡。由于新出现的耐药性，溶组织内阿米巴是西雅图传染病结构基因组学中心（SSGCID）基于结构的药物研发的目标生物之一。本文介绍了来自溶组织内阿米巴的假定药物靶标核糖核酸内切酶L-PSP（EhL-PSP）的纯化、结晶及三种结构。EhL-PSP具有两层α/β三明治结构，与核糖核酸内切酶L-PSP具有结构同源性。所有三种结构均揭示了典型的YjgF/YER057c/UK114家族三聚体拓扑结构以及可及的别构活性位点。在报道的三种结构中的两种结构中，来自结晶溶液的柠檬酸盐分子结合到别构位点。EhL-PSP的大的别构位点与细菌YjgF/YER057c/UK114家族成员高度保守，可作为抑制、药物研发或药物重新利用的靶点。
