2za5 | pdb_00002za5
Crystal Structure of human tryptase with potent non-peptide inhibitor
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| 2za5, resolution 2.300Å | |||||||||||||
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| Sites: | AC1, AC2, AC3 and AC4 | ||||||||||||
| Ligands: | 2FF | ||||||||||||
| Activity: | Tryptase, with EC number 3.4.21.59 | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.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.
About this Structure
2ZA5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Jan 30;. PMID:18272363
Page seeded by OCA on Mon Mar 31 05:19:51 2008
