6ahs | pdb_00006ahs
Mouse Kallikrein 7 in complex with imidazolinylindole derivative
Structural highlights
FunctionKLK7_MOUSE May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. Cleaves insulin A chain at '14-Tyr-|-Gln-15' and insulin B chain at '6-Leu-|-Cys-7', '16-Tyr-|-Leu-17', '25-Phe-|-Tyr-26' and '26-Tyr-|-Thr-27'. Could play a role in the activation of precursors to inflammatory cytokines. Publication Abstract from PubMedA series of imidazolinylindole derivatives were discovered as novel kallikrein 7 (KLK7, stratum corneum chymotryptic enzyme) inhibitors. Structure-activity relationship (SAR) studies led to the identification of potent human KLK7 inhibitors. By further modification of the benzenesulfonyl moiety to overcome species differences in inhibitory activity, potent inhibitors against both human and mouse KLK7 were identified. Furthermore, the complex structure of 25 with mouse KLK7 could explain the SAR and the cause of the species differences in inhibitory activity. Discovery and structure-activity relationship of imidazolinylindole derivatives as kallikrein 7 inhibitors.,Murafuji H, Muto T, Goto M, Imajo S, Sugawara H, Oyama Y, Minamitsuji Y, Miyazaki S, Murai K, Fujioka H Bioorg Med Chem Lett. 2019 Jan 15;29(2):334-338. doi: 10.1016/j.bmcl.2018.11.011., Epub 2018 Nov 8. PMID:30522951[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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