6KR5

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

Summary for 6KR5

• Entry DOI: 10.2210/pdb6kr5/pdb
• Descriptor: Cysteine synthase 3, PYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• Functional Keywords: o-acetylserine sulphydralase, cysteine synthase transferase o-acetyl-l-serine(thiol)lyase, transferase
• Biological source: Entamoeba histolytica
• Total number of polymer chains: 2
• Total formula weight: 73476.60

Authors

Dharavath, S.,Gourinath, S. (deposition date: 2019-08-21, release date: 2020-09-09, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.544 Å)