- PDB-6pbe: ZINC17988990-bound TRPV5 in nanodiscs -
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基本情報
登録情報
データベース: PDB / ID: 6pbe
タイトル
ZINC17988990-bound TRPV5 in nanodiscs
要素
Transient receptor potential cation channel subfamily V member 5
キーワード
TRANSPORT PROTEIN / TRPV5 / TRP Channel / Inhibitor / Calcium channel
機能・相同性
機能・相同性情報
regulation of urine volume / calcium ion import across plasma membrane / calcium ion homeostasis / calcium ion transmembrane transport / calcium channel activity / calcium ion transport / protein homotetramerization / calmodulin binding / apical plasma membrane / identical protein binding ...regulation of urine volume / calcium ion import across plasma membrane / calcium ion homeostasis / calcium ion transmembrane transport / calcium channel activity / calcium ion transport / protein homotetramerization / calmodulin binding / apical plasma membrane / identical protein binding / metal ion binding / plasma membrane 類似検索 - 分子機能
Transient receptor potential cation channel subfamily V member 5 / Transient receptor potential cation channel subfamily V member 5/6 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily ...Transient receptor potential cation channel subfamily V member 5 / Transient receptor potential cation channel subfamily V member 5/6 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Ion transport domain / Ion transport protein 類似検索 - ドメイン・相同性
Chem-O6S / Transient receptor potential cation channel subfamily V member 5 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM103899
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM129357
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM093290
米国
引用
ジャーナル: Elife / 年: 2019 タイトル: Structure-based characterization of novel TRPV5 inhibitors. 著者: Taylor Et Hughes / John Smith Del Rosario / Abhijeet Kapoor / Aysenur Torun Yazici / Yevgen Yudin / Edwin C Fluck / Marta Filizola / Tibor Rohacs / Vera Y Moiseenkova-Bell / 要旨: Transient receptor potential vanilloid 5 (TRPV5) is a highly calcium selective ion channel that acts as the rate-limiting step of calcium reabsorption in the kidney. The lack of potent, specific ...Transient receptor potential vanilloid 5 (TRPV5) is a highly calcium selective ion channel that acts as the rate-limiting step of calcium reabsorption in the kidney. The lack of potent, specific modulators of TRPV5 has limited the ability to probe the contribution of TRPV5 in disease phenotypes such as hypercalcemia and nephrolithiasis. Here, we performed structure-based virtual screening (SBVS) at a previously identified TRPV5 inhibitor binding site coupled with electrophysiology screening and identified three novel inhibitors of TRPV5, one of which exhibits high affinity, and specificity for TRPV5 over other TRP channels, including its close homologue TRPV6. Cryo-electron microscopy of TRPV5 in the presence of the specific inhibitor and its parent compound revealed novel binding sites for this channel. Structural and functional analysis have allowed us to suggest a mechanism of action for the selective inhibition of TRPV5 and lay the groundwork for rational design of new classes of TRPV5 modulators.