6yya

Crystal structure of SAICAR Synthetase (PurC) from Mycobacterium abscessus in complex with inhibitor

spinqualitylabelsall models 6yya, resolution 1.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6yya is a 1 chain structure with sequence from Mycobacteroides abscessus ATCC 19977. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.41Å Ligands: EDO, PZK, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PUR7_MYCA9 Publication Abstract from PubMed Mycobacterium abscessus (Mab) has emerged as a challenging threat to individuals with cystic fibrosis. Infections caused by this pathogen are often impossible to treat due to the intrinsic antibiotic resistance leading to lung malfunction and eventually death. Therefore, there is an urgent need to develop new drugs against novel targets in Mab to overcome drug resistance and subsequent treatment failure. In this study, SAICAR synthetase (PurC) from Mab was identified as a promising target for novel antibiotics. An in-house fragment library screen and a high-throughput X-ray crystallographic screen of diverse fragment libraries were explored to provide crucial starting points for fragment elaboration. A series of compounds developed from fragment growing and merging strategies, guided by crystallographic information and careful hit-to-lead optimization, have achieved potent nanomolar binding affinity against the enzyme. Some compounds also show a promising inhibitory effect against Mab and Mtb. This work utilizes a fragment-based design and demonstrates for the first time the potential to develop inhibitors against PurC from Mab. Development of Inhibitors of SAICAR Synthetase (PurC) from Mycobacterium abscessus Using a Fragment-Based Approach.,Charoensutthivarakul S, Thomas SE, Curran A, Brown KP, Belardinelli JM, Whitehouse AJ, Acebron-Garcia-de-Eulate M, Sangan J, Gramani SG, Jackson M, Mendes V, Floto RA, Blundell TL, Coyne AG, Abell C ACS Infect Dis. 2022 Feb 11;8(2):296-309. doi: 10.1021/acsinfecdis.1c00432. Epub , 2022 Jan 17. PMID:35037462 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also SAICAR synthetase

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