In this review, we describe the creation of the Nucleic Acid Database (NDB) at Rutgers University and how it became a testbed for the current infrastructure of the RCSB Protein Data Bank. We describe some of the special features of the NDB and how it has been used to enable research. Plans for the next phase as the Nucleic Acid Knowledgebase (NAKB) are summarized.
- Klíčová slova
- DNA, RNA, biological structure database, nucleic acid conformation, nucleic acid structures, validation standards,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Histone deacetylase 6 (HDAC6) is a promising therapeutic target for the treatment of neurodegenerative disorders. SW-100 (1a), a phenylhydroxamate-based HDAC6 inhibitor (HDAC6i) bearing a tetrahydroquinoline (THQ) capping group, is a highly potent and selective HDAC6i that was shown to be effective in mouse models of Fragile X syndrome and Charcot-Marie-Tooth disease type 2A (CMT2A). In this study, we report the discovery of a new THQ-capped HDAC6i, termed SW-101 (1s), that possesses excellent HDAC6 potency and selectivity, together with markedly improved metabolic stability and druglike properties compared to SW-100 (1a). X-ray crystallography data reveal the molecular basis of HDAC6 inhibition by SW-101 (1s). Importantly, we demonstrate that SW-101 (1s) treatment elevates the impaired level of acetylated α-tubulin in the distal sciatic nerve, counteracts progressive motor dysfunction, and ameliorates neuropathic symptoms in a CMT2A mouse model bearing mutant MFN2. Taken together, these results bode well for the further development of SW-101 (1s) as a disease-modifying HDAC6i.
- MeSH
- acetylace MeSH
- benzamidy chemie metabolismus MeSH
- Charcotova-Marieova-Toothova nemoc farmakoterapie metabolismus patologie MeSH
- chinoliny chemie metabolismus terapeutické užití MeSH
- fenotyp MeSH
- histondeacetylasa 6 antagonisté a inhibitory metabolismus MeSH
- inhibitory histondeacetylas chemie metabolismus terapeutické užití MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- poločas MeSH
- protein - isoformy antagonisté a inhibitory metabolismus MeSH
- simulace molekulového dockingu MeSH
- tubulin metabolismus MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- 1,2,3,4-tetrahydroquinoline MeSH Prohlížeč
- benzamidy MeSH
- chinoliny MeSH
- histondeacetylasa 6 MeSH
- inhibitory histondeacetylas MeSH
- protein - isoformy MeSH
- SW-100 MeSH Prohlížeč
- tubulin MeSH
