Találati lista | Tudóstér

001-es BibID:	BIBFORM080522
035-os BibID:	(WOS)000480733000011 (Scopus)85071351221 (PMID)31337666
Első szerző:	Diszházi Gyula (gyógyszerész)
Cím:	Dantrolene Requires Mg2+ and ATP To Inhibit the Ryanodine Receptor / Gyula Diszházi, Zsuzsanna Édua Magyar, János András Mótyán, László Csernoch, István Jóna, Péter Pál Nánási, János Almássy
Dátum:	2019
ISSN:	0026-895X
Megjegyzések:	Dantrolene is a ryanodine receptor (RyR) inhibitor, which is used to relax muscles in malignant hyperthermia syndrome. Although dantrolene binds to the RyR protein, its mechanism of action is unknown, mainly because of the controversial results showing that dantrolene inhibited Ca2+ release from intact fibers and sarcoplasmic reticulum (SR) vesicles, but failed to inhibit single RyR channel currents in bilayers. Accordingly, it was concluded that an important factor for dantrolene's action was lost during the purification procedure of RyR. Recently, Mg2+ was demonstrated to be the essential factor for dantrolene to inhibit Ca2+ release in skinned muscle fibers. The aim of the present study was confirm these results in Ca2+ release and bilayer experiments, using SR vesicles and solubilized channels, respectively. Our Ca2+ release experiments demonstrated that the effect of dantrolene and Mg2+ was cooperative and that ATP enhanced the inhibiting effect of dantrolene. Namely, 10 mu M dantrolene reduced RyR channel open probability by similar to 50% in the presence of 3 mM free Mg2+ and 1 mMATP, whereas channel activity further decreased to similar to 20% of control when [ATP] was increased to 2 mM. Our data provide important complementary information that supports the direct, Mg2+-dependent mechanism of dantrolene's action and suggests that dantrolene also requires ATP to inhibit RyR.
Tárgyszavak:	idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Molecular Pharmacology. - 96 : 3 (2019), p. 401-407. -
További szerzők:	Magyar Zsuzsanna Édua (1993-) (molekuláris biológus) Mótyán János András (1981-) (biokémikus, molekuláris biológus) Csernoch László (1961-) (élettanász) Jóna István (1948-) (élettanász, fizikus) Nánási Péter Pál (1956-) (élettanász) Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító)
Pályázati támogatás:	PD112199 OTKA K115397 OTKA GINOP-2.3.2-15-2016-00040 GINOP EFOP-3.6.2-16-2017-00006 EFOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:

001-es BibID:	BIBFORM052923
Első szerző:	Luna-Ramirez, Karen
Cím:	Structure, Molecular Modeling, and Function of the Novel Potassium Channel Blocker Urotoxin Isolated from the Venom of the Australian Scorpion Urodacus yaschenkoi / Karen Luna-Ramirez, Adam Bartok, Rita Restano-Cassulini, Veronica Quintero-Hernández, Fredy I. V. Coronas, Janni Christensen, Christine E. Wright, Gyorgy Panyi, Lourival D. Possani
Dátum:	2014
ISSN:	1521-0111
Megjegyzések:	This communication reports the structural and functional characterization of urotoxin, the first K(+) channel toxin isolated from the venom of the Australian scorpion Urodacus yaschenkoi. It is a basic peptide consisting of 37 amino acids with an amidated C-terminal residue. Urotoxin contains eight cysteines forming four disulfide bridges with sequence similarities resembling the ?-potassium channel toxin 6 (?-KTx-6) subfamily of peptides; it was assigned the systematic number of ?-KTx-6.21. Urotoxin is a potent blocker of human voltage-gated potassium channel (Kv)1.2 channels, with an IC50 of 160 pM, whereas its affinity for other channels tested was in the nanomolar range (hKv1.1, IC50 = 253 nM; hKv1.3, IC50 = 91 nM; and hKCa3.1, IC50 = 70 nM). The toxin had no effect on hKv1.4, hKv1.5, human ether-ℓa-go-go-related gene type 1 (hERG1), or human ether-ℓa-go-go-like (hELK2) channels. Multiple sequence alignments from the venom gland transcriptome showed the existence of four other new peptides similar to urotoxin. Computer modeling of urotoxin's three-dimensional structure suggests the presence of the ?/?-scaffold characteristic of other scorpion toxins, although very likely forming an uncommon disulfide pairing pattern. Using molecular dynamics, a model for the binding of this peptide to human Kv1.2 and hKv1.1 channels is presented, along with the binding of an in silico mutant urotoxin (Lys25Ala) to both channels. Urotoxin enriches our knowledge of K(+) channel toxins and, due to its high affinity for hKv1.2 channels, it may be a good candidate for the development of pharmacologic tools to study the physiologic functions of K(+) channels or related channelopathies and for restoring axonal conduction in demyelinated axons.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban scorpion toxin potassium channel
Megjelenés:	Molecular Pharmacology. - 86 : 1 (2014), p. 28-41. -
További szerzők:	Bartók Ádám (1984-) (biotechnológus) Restano-Cassulini, Rita Quintero-Hernandez, Veronica Coronas, Fredy I. V. Christensen, Janni Wright, Christine E. Panyi György (1966-) (biofizikus) Possani, Lourival Domingos
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: