5ezh

Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound 21 at 1.7A resolution

spinqualitylabelsall models 5ezh, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ezh is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 841, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ETHR_MYCTO] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH). Publication Abstract from PubMed With the ever-increasing instances of resistance to frontline TB drugs there is the need to develop novel strategies to fight the worldwide TB epidemic. Boosting the effect of the existing second-line antibiotic ethionamide by inhibiting the mycobacterial transcriptional repressor protein EthR is an attractive therapeutic strategy. Herein we report the use of a fragment based drug discovery approach for the structure-guided systematic merging of two fragment molecules, each binding twice to the hydrophobic cavity of EthR from M. tuberculosis. These together fill the entire binding pocket of EthR. We elaborated these fragment hits and developed small molecule inhibitors which have a 100-fold improvement of potency in vitro over the initial fragments. A fragment merging approach towards the development of small molecule inhibitors of Mycobacterium tuberculosis EthR for use as ethionamide boosters.,Nikiforov PO, Surade S, Blaszczyk M, Delorme V, Brodin P, Baulard AR, Blundell TL, Abell C Org Biomol Chem. 2016 Jan 25. PMID:26806381 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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