2ZA5
Crystal Structure of human tryptase with potent non-peptide inhibitor
Summary for 2ZA5
| Entry DOI | 10.2210/pdb2za5/pdb |
| Descriptor | Tryptase beta 2, (5-(aminomethyl)-2H-spiro[benzofuran-3,4'-piperidine]-1'-yl)(5-(phenylethynyl)furan-2-yl)methanone (3 entities in total) |
| Functional Keywords | tryptase, serine protease, tetramer, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 111615.62 |
| Authors | Spurlino, J.C.,Barnakov, S.A.,Lewandowski, F.,Milligan, C. (deposition date: 2007-10-02, release date: 2008-02-26, Last modification date: 2024-10-30) |
| Primary citation | Costanzo, M.J.,Yabut, S.C.,Zhang, H.-C.,White, K.B.,de Garavilla, L.,Wang, Y.,Minor, L.K.,Tounge, B.A.,Barnakov, A.N.,Lewandowski, F.,Milligan, C.,Spurlino, J.C.,Abraham, W.M.,Boswell-Smith, V.,Page, C.P.,Maryanoff, B.E. Potent, nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives Bioorg.Med.Chem.Lett., 18:2114-2121, 2008 Cited by PubMed Abstract: We 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. PubMed: 18272363DOI: 10.1016/j.bmcl.2008.01.093 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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