6SKD

Crystal Structure of Human Kallikrein 6 (I218Y) in complex with GSK3397892A

6SKD の概要

• エントリーDOI: 10.2210/pdb6skd/pdb
• 分子名称: Kallikrein-6, UNKNOWN ATOM OR ION, 4-[[(3~{S})-1-oxidanyl-3,4-dihydro-2,1-benzoxaborinin-3-yl]methylamino]benzenecarboximidamide, ... (5 entities in total)
• 機能のキーワード: protease, inhibitor, complex, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49709.90

構造登録者

Thorpe, J.H. (登録日: 2019-08-15, 公開日: 2019-09-25, 最終更新日: 2024-10-23)

主引用文献

Walker, A.L.,Denis, A.,Bingham, R.P.,Boulliot, A.,Edgar, E.V.,Ferrie, A.,Holmes, D.S.,Laroze, A.,Liddle, J.,Fouchet, M.H.,Moquette, A.,Nassau, P.,Pearce, A.C.,Polyakova, O.,Smith, K.J.,Thomas, P.,Thorpe, J.H.,Trottet, L.,Wang, Y.,Hovnanian, A.
Design and development of a series of borocycles as selective, covalent kallikrein 5 inhibitors.
Bioorg.Med.Chem.Lett., 29:126675-126675, 2019

PubMed Abstract: The connection between Netherton syndrome and overactivation of epidermal/dermal proteases, particularly Kallikrein 5 (KLK5) has been well established and it is expected that a KLK5 inhibitor would improve the dermal barrier and also reduce the pain and itch that afflict Netherton syndrome patients. One of the challenges of covalent protease inhibitors has been achieving selectivity over closely related targets. In this paper we describe the use of structural insight to design and develop a selective and highly potent reversibly covalent KLK5 inhibitor from an initial weakly binding fragment.

PubMed: 31521475
DOI: 10.1016/j.bmcl.2019.126675

実験手法

X-RAY DIFFRACTION (2.26 Å)