3VFE

Virtual Screening and X-Ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group

Summary for 3VFE

• Entry DOI: 10.2210/pdb3vfe/pdb
• Descriptor: Kallikrein-6, 4-{[(3R)-3-{[(7-methoxynaphthalen-2-yl)sulfonyl](thiophen-3-ylmethyl)amino}-2-oxopyrrolidin-1-yl]methyl}thiophene-2-carboximidamide (3 entities in total)
• Functional Keywords: human kallikrein 6, hk6, serine protease, protein-ligand complex, amidinothiophene, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: Q92876
• Total number of polymer chains: 1
• Total formula weight: 24972.40

Authors

Chen, X.,Zhang, Y.,Xia, T.,Wang, R. (deposition date: 2012-01-09, release date: 2012-11-21, Last modification date: 2024-11-06)

Primary citation

Liang, G.,Chen, X.,Aldous, S.,Pu, S.F.,Mehdi, S.,Powers, E.,Giovanni, A.,Kongsamut, S.,Xia, T.,Zhang, Y.,Wang, R.,Gao, Z.,Merriman, G.,McLean, L.R.,Morize, I.
Virtual Screening and X-ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group.
Acs Med.Chem.Lett., 3:159-164, 2012

PubMed Abstract: A series of compounds with an amidinothiophene P1 group and a pyrrolidinone-sulphonamide scaffold linker was identified as potent inhibitors of human kallikrein 6 by structure-based virtual screening based on the union accessible binding space of serine proteases. As the first series of potent nonmechanism-based hK6 inhibitors, they may be used as tool compounds for target validation. An X-ray structure of a representative compound complexed with hK6, resolved at a resolution of 1.88 Å, revealed that the amidinothiophene moiety bound in the S1 pocket and the pyrrolidinone-sulphonamide linker projected the aromatic tail into the S' pocket.

PubMed: 24900446
DOI: 10.1021/ml200291e

Experimental method

X-RAY DIFFRACTION (1.88 Å)