Pub. Date : 2015 Mar 10
PMID : 25762321
4 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | We previously reported that the bis-nitro-phenyl ROMK inhibitor VU591 exhibits voltage-dependent knock-off at hyperpolarizing potentials, suggesting that the binding site is located within the ion-conduction pore. | VU591 | potassium inwardly rectifying channel subfamily J member 1 | Homo sapiens |
| 2 | In this study, comparative molecular modeling and in silico ligand docking were used to interrogate the full-length ROMK pore for energetically favorable VU591 binding sites. | VU591 | potassium inwardly rectifying channel subfamily J member 1 | Homo sapiens |
| 3 | Cluster analysis of 2498 low-energy poses resulting from 9900 Monte Carlo docking trajectories on each of 10 conformationally distinct ROMK comparative homology models identified two putative binding sites in the transmembrane pore that were subsequently tested for a role in VU591-dependent inhibition using site-directed mutagenesis and patch-clamp electrophysiology. | VU591 | potassium inwardly rectifying channel subfamily J member 1 | Homo sapiens |
| 4 | In contrast, mutations of Val(168) or Asn(171) in the upper site, which are unique to ROMK within the Kir channel family, led to a dramatic reduction in VU591 sensitivity. | VU591 | potassium inwardly rectifying channel subfamily J member 1 | Homo sapiens |