Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

5FUE

Crystal structure of Schistosoma mansoni HDAC8 complexed with 3- benzamido-benzohydroxamate

Summary for 5FUE
Entry DOI10.2210/pdb5fue/pdb
DescriptorHISTONE DEACETYLASE 8, ZINC ION, POTASSIUM ION, ... (7 entities in total)
Functional Keywordshydrolase, platyhelminths, inhibition, histone, deacetylation
Biological sourceSCHISTOSOMA MANSONI
Total number of polymer chains4
Total formula weight204565.20
Authors
Marek, M.,Romier, C. (deposition date: 2016-01-26, release date: 2016-03-09, Last modification date: 2024-05-08)
Primary citationHeimburg, T.,Chakrabarti, A.,Lancelot, J.,Marek, M.,Melesina, J.,Hauser, A.T.,Shaik, T.B.,Duclaud, S.,Robaa, D.,Erdmann, F.,Schmidt, M.,Romier, C.,Pierce, R.J.,Jung, M.,Sippl, W.
Structure-Based Design and Synthesis of Novel Inhibitors Targeting Hdac8 from Schistosoma Mansoni for the Treatment of Schistosomiasis.
J.Med.Chem., 59:2423-, 2016
Cited by
PubMed Abstract: Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (1 and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture.
PubMed: 26937828
DOI: 10.1021/ACS.JMEDCHEM.5B01478
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.199 Å)
Structure validation

239149

건을2025-07-23부터공개중

PDB statisticsPDBj update infoContact PDBjnumon