2za5
From Proteopedia
Crystal Structure of human tryptase with potent non-peptide inhibitor
Structural highlights
FunctionTRYB2_HUMAN Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. Has an immunoprotective role during bacterial infection. Required to efficiently combat K.pneumoniae infection (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe have explored a series of spirocyclic piperidine amide derivatives (5) as tryptase inhibitors. Thus, 4 (JNJ-27390467) was identified as a potent, selective tryptase inhibitor with oral efficacy in two animal models of airway inflammation (sheep and guinea pig asthma models). An X-ray co-crystal structure of 4 x tryptase revealed a hydrophobic pocket in the enzyme's active site, which is induced by the phenylethynyl group and is comprised of amino acid residues from two different monomers of the tetrameric protein. Potent, nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives.,Costanzo MJ, Yabut SC, Zhang HC, White KB, de Garavilla L, Wang Y, Minor LK, Tounge BA, Barnakov AN, Lewandowski F, Milligan C, Spurlino JC, Abraham WM, Boswell-Smith V, Page CP, Maryanoff BE Bioorg Med Chem Lett. 2008 Mar 15;18(6):2114-21. Epub 2008 Jan 30. PMID:18272363[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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