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Page 1
An Update on the Structure of hERG.
Butler A, Helliwell MV, Zhang Y, Hancox JC, Dempsey CE. Butler A, et al. Front Pharmacol. 2020 Jan 24;10:1572. doi: 10.3389/fphar.2019.01572. eCollection 2019. Front Pharmacol. 2020. PMID: 32038248 Free PMC article. Review.
Inherited loss- or gain-of-function mutations in hERG can result in dangerous "long" (LQTS) or "short" QT syndromes (SQTS), respectively, and the anomalous susceptibility of hERG to block by a diverse range of drugs underlies an acquired LQTS. A recent open channel cryo-EM …
Inherited loss- or gain-of-function mutations in hERG can result in dangerous "long" (LQTS) or "short" QT syndromes (SQTS), respectively, an …
Electrophysiological characterization of the modified hERG(T) potassium channel used to obtain the first cryo-EM hERG structure.
Zhang Y, Dempsey CE, Hancox JC. Zhang Y, et al. Physiol Rep. 2020 Oct;8(20):e14568. doi: 10.14814/phy2.14568. Physiol Rep. 2020. PMID: 33091232 Free PMC article.
Loss-of-function mutations or pharmacological inhibition of hERG leads to long QT syndrome, whilst gain-of-function mutations lead to short QT syndrome. A recent open channel cryo-EM structure of hERG represents a significant advance in the ability to interrogate hERG chan …
Loss-of-function mutations or pharmacological inhibition of hERG leads to long QT syndrome, whilst gain-of-function mutations lead to short …
Potent hERG channel inhibition by sarizotan, an investigative treatment for Rett Syndrome.
Cheng H, Du C, Zhang Y, James AF, Dempsey CE, Abdala AP, Hancox JC. Cheng H, et al. J Mol Cell Cardiol. 2019 Oct;135:22-30. doi: 10.1016/j.yjmcc.2019.07.012. Epub 2019 Jul 27. J Mol Cell Cardiol. 2019. PMID: 31362019 Free PMC article.
Docking analysis was conducted using a recent cryo-EM structure of hERG. Sarizotan was a potent inhibitor of hERG current (I(hERG); IC(50) of 183 nM) and of native ventricular I(Kr) from guinea-pig ventricular myocytes. 100 nM and 1 muM sarizotan prolonged ventricular acti …
Docking analysis was conducted using a recent cryo-EM structure of hERG. Sarizotan was a potent inhibitor of hERG current (I(hERG); I …
Structural implications of hERG K+ channel block by a high-affinity minimally structured blocker.
Helliwell MV, Zhang Y, El Harchi A, Du C, Hancox JC, Dempsey CE. Helliwell MV, et al. J Biol Chem. 2018 May 4;293(18):7040-7057. doi: 10.1074/jbc.RA117.000363. Epub 2018 Mar 15. J Biol Chem. 2018. PMID: 29545312 Free PMC article.
Computational docking using the recent cryo-EM structure of an open channel hERG construct could only partially recapitulate experimental data, and the high dependence of Cavalli-2 block on Phe-656 is not readily explainable in that structure. A small clockwise rotation of …
Computational docking using the recent cryo-EM structure of an open channel hERG construct could only partially recapitulate experime …
Inhibition of the hERG potassium channel by phenanthrene: a polycyclic aromatic hydrocarbon pollutant.
Al-Moubarak E, Shiels HA, Zhang Y, Du C, Hanington O, Harmer SC, Dempsey CE, Hancox JC. Al-Moubarak E, et al. Cell Mol Life Sci. 2021 Dec;78(23):7899-7914. doi: 10.1007/s00018-021-03967-8. Epub 2021 Nov 2. Cell Mol Life Sci. 2021. PMID: 34727194 Free PMC article.
In contrast, the F557L (S5) and M651A (S6) mutations impaired the ability of phenanthrene to inhibit I(hERG), as did the S624A mutation below the selectivity filter region. Computational docking using a cryo-EM derived hERG structure supported the mutagenesis data. Thus, p …
In contrast, the F557L (S5) and M651A (S6) mutations impaired the ability of phenanthrene to inhibit I(hERG), as did the S624A mutation belo …
Functional and pharmacological characterization of an S5 domain hERG mutation associated with short QT syndrome.
Butler A, Zhang Y, Stuart AG, Dempsey CE, Hancox JC. Butler A, et al. Heliyon. 2019 Apr 20;5(4):e01429. doi: 10.1016/j.heliyon.2019.e01429. eCollection 2019 Apr. Heliyon. 2019. PMID: 31049424 Free PMC article.
Whole cell patch clamp recordings of wild-type (WT) and I560T hERG current (I(hERG)) were made at 37 C from hERG expressing HEK 293 cells, and the structural context of the mutation was investigated using a recently reported cryo-EM structure of hERG. Under conventional v …
Whole cell patch clamp recordings of wild-type (WT) and I560T hERG current (I(hERG)) were made at 37 C from hERG expressing HEK 293 cells, …
In silico Exploration of Interactions Between Potential COVID-19 Antiviral Treatments and the Pore of the hERG Potassium Channel-A Drug Antitarget.
Al-Moubarak E, Sharifi M, Hancox JC. Al-Moubarak E, et al. Front Cardiovasc Med. 2021 May 4;8:645172. doi: 10.3389/fcvm.2021.645172. eCollection 2021. Front Cardiovasc Med. 2021. PMID: 34017865 Free PMC article.
Methods: Atazanavir, remdesivir, ritonavir, lopinavir and favipiravir were docked to in silico models of the pore domain of hERG, derived from cryo-EM structures of hERG and the closely related EAG channel. Results: Atazanavir was readily accommodated in the open hERG chan …
Methods: Atazanavir, remdesivir, ritonavir, lopinavir and favipiravir were docked to in silico models of the pore domain of hERG, derived fr …
15 results