Key Publications and online material
The molecular basis of drug selectivity for alpha5 subunit-containing GABAA receptors.
Kasaragod VB, Malinauskas T, Wahid AA, Lengyel J, Knoflach F, Hardwick SW, Jones CF, Chen W-N, Lucas X, Omari K, Chirgadze DY, Aricescu AR, Cecere G, Hernandez M-C, Miller PS.
Nature Structure and Molecular Biology, 2023, Dec, 30(12), p. 1936-1946. PMID: 37903907.
https://www.nature.com/articles/s41594-023-01133-1
HIGHLIGHTS:
1) Engineered GABA-A a5 receptor for drug design
2) Basis of a5 selectivity for b-carbolines, benzodiazepines and isoxazoles revealed
3) Ligands displacements oberved between isoxazole negative vs positive modulators
Mechanisms of inhibition and activation of extrasynaptic alpha-beta GABAA receptors.
Vikram B. Kasaragod, Martin Mortensen, Steven W. Hardwick, Ayla A. Wahid, Valentina Dorovykh, Dimitri Y. Chirgadze, Trevor G. Smart, Paul S. Miller. Nature, 2022, Feb, 602(7897), p. 529-533. PMID: 35140402. https://www.nature.com/articles/s41586-022-04402-z
HIGHLIGHTS:
1) GABA-A receptor bound by alpha-Cobratoxin
2) Molecular mechanism of inhibition by zinc
3) Observation of a low efficacy GABA-bound conformation
Heteromeric GABAA receptor structures in positively-modulated active states.
Miller. PS, Masiulis. S, Malinauskas T, Kotecha. A, Rao. S, Chavali. S, De Colibus. L, Pardon. E, Hannan. S, Scott. S, Sun. Z, Frenz. B, Klesse. G, Li. S, Diprose. DM, Siebert. AC, Esnouf. RM, DiMaio. F, Tucker. SJ, Smart. TG, Steyaert. J, Babu. MM, Sansom. MSP, Huiskonen. JT, Aricescu. AR. Biorxiv, 2018. https://www.biorxiv.org/content/early/2018/06/05/338343
Structural basis for GABAA receptor potentiation by neurosteroids.
Miller. PS, Scott. S, Masiulis. S, De Colibus. L, Pardon. E, Steyaert. J, Aricescu. AR.
Nature Structure and Molecular Biology. 2017, 24(11), p. 986-992.
Structural basis of Smoothened regulation by its extracellular domains.
Byrne. EFX, Sircar. R, Miller. PS, Hedger. G, Luchetti. G, Nachtergaele. S, Tully. MD, Mydock-McGrane. L, Covey. DF, Rambo. RP, Sansom. MSP, Newstead. S, Rohatgi. R, Siebold. C.
Nature. 2016, 535, p. 517-522.
Crystal structure of a human GABAAR.
Miller. PS, Aricescu. AR.
Nature. 2014, 512, p. 270-275.
Cys-loop Receptors: Activation and Modulation.
Miller. PS, Smart TG.
Trends in Pharmacological Sciences. 2010, 31, 4, p.161.