5a2s

Potent, selective and CNS-penetrant tetrasubstituted cyclopropane class IIa histone deacetylase (HDAC) inhibitors

spinqualitylabelsall models 5a2s, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5a2s is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.65Å Ligands: NA, OTF, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HDAC4_HUMAN Defects in HDAC4 are the cause of brachydactyly-mental retardation syndrome (BDMR) [MIM:600430. A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism. Function HDAC4_HUMAN Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Publication Abstract from PubMed Potent and selective class IIa HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class IIa HDAC catalytic site inhibition in preclinical disease models. Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors.,Luckhurst CA, Breccia P, Stott AJ, Aziz O, Birch HL, Burli RW, Hughes SJ, Jarvis RE, Lamers M, Leonard PM, Matthews KL, McAllister G, Pollack S, Saville-Stones E, Wishart G, Yates D, Dominguez C ACS Med Chem Lett. 2015 Dec 10;7(1):34-9. doi: 10.1021/acsmedchemlett.5b00302., eCollection 2016 Jan 14. PMID:26819662 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone deacetylase 3D structures

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