6SKB

Crystal Structure of Human Kallikrein 6 (N217D/I218Y/K224R) in complex with GSK3496783A

Summary for 6SKB

• Entry DOI: 10.2210/pdb6skb/pdb
• Descriptor: Kallikrein-6, 4-[(3~{S})-1-oxidanyl-3,4-dihydro-2,1-benzoxaborinin-3-yl]-2-(pyridin-3-ylmethoxy)benzenecarboximidamide, 4-[(3~{R})-1-oxidanyl-3,4-dihydro-2,1-benzoxaborinin-3-yl]-2-(pyridin-3-ylmethoxy)benzenecarboximidamide, ... (5 entities in total)
• Functional Keywords: protease, inhibitor, complex, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 96553.93

Authors

Thorpe, J.H. (deposition date: 2019-08-15, release date: 2019-09-25, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.84 Å)