6KR5

Crystal structure of O-Acetyl Serine Sulfhydrylase isoform 3 from Entamoeba histolytica

6KR5 の概要

• エントリーDOI: 10.2210/pdb6kr5/pdb
• 分子名称: Cysteine synthase 3, PYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• 機能のキーワード: o-acetylserine sulphydralase, cysteine synthase transferase o-acetyl-l-serine(thiol)lyase, transferase
• 由来する生物種: Entamoeba histolytica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73476.60

構造登録者

Dharavath, S.,Gourinath, S. (登録日: 2019-08-21, 公開日: 2020-09-09, 最終更新日: 2023-11-22)

主引用文献

Dharavath, S.,Vijayan, R.,Kumari, K.,Tomar, P.,Gourinath, S.
Crystal structure of O-Acetylserine sulfhydralase (OASS) isoform 3 from Entamoeba histolytica: Pharmacophore-based virtual screening and validation of novel inhibitors.
Eur.J.Med.Chem., 192:112157-112157, 2020

PubMed Abstract: The l-cysteine is crucial for growth, survival, defense against oxidative stress, and pathogenesis of Entamoeba histolytica. The de novo biosynthesis of l-cysteine in E. histolytica, has a two-step pathway, where O-acetylserine sulfhydrylase (OASS) catalyses the last step by converting OAS to l-cysteine. This pathway is absent in humans and hence represents a promising target for novel therapeutics. E. histolytica expresses three isoforms of OASS and knockdown studies showed the importance of these enzymes for the survival of the pathogen. Here, we report the crystal structure of OASS isoform 3 from E. histolytica to 1.54 Å resolution. The active site geometries and kinetics of EhOASS3 and EhOASS1 structures were found to be very similar. Small-molecule libraries were screened against EhOASS3 and compounds were shortlisted based on the docking scores. F3226-1387 showed best inhibition with IC of 38 μM against EhOASS3 and was able to inhibit the growth of the organism to 72%.

PubMed: 32145643
DOI: 10.1016/j.ejmech.2020.112157

実験手法

X-RAY DIFFRACTION (1.544 Å)