4A6L
beta-tryptase inhibitor
Summary for 4A6L
| Entry DOI | 10.2210/pdb4a6l/pdb |
| Related | 1AAO |
| Descriptor | TRYPTASE ALPHA/BETA-1, 1-{3-[1-({5-[(2-fluorophenyl)ethynyl]furan-2-yl}carbonyl)piperidin-4-yl]phenyl}methanamine (3 entities in total) |
| Functional Keywords | hydrolase, inhibitor |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Secreted: Q15661 |
| Total number of polymer chains | 4 |
| Total formula weight | 111575.55 |
| Authors | Mathieu, M.,Maignan, S. (deposition date: 2011-11-04, release date: 2012-01-25, Last modification date: 2024-11-06) |
| Primary citation | Liang, G.,Aldous, S.,Merriman, G.,Levell, J.,Pribish, J.,Cairns, J.,Chen, X.,Maignan, S.,Mathieu, M.,Tsay, J.,Sides, K.,Rebello, S.,Whitely, B.,Morize, I.,Pauls, H.W. Structure-Based Library Design and the Discovery of a Potent and Selective Mast Cell Beta-Tryptase Inhibitor as an Oral Therapeutic Agent. Bioorg.Med.Chem.Lett., 22:1049-, 2012 Cited by PubMed Abstract: A solid phase combinatorial library was designed based on X-ray structures and in-silico models to explore an inducible S4+ pocket, which is formed by a simple side-chain rotation of Tyr95. This inducible S4+ pocket is unique to β-tryptase and does not exist for other trypsin-like serine proteases of interest. Therefore, inhibitors utilizing this pocket have inherent advantages for being selective against other proteases in the same family. A member of this library was found to be a potent and selective β-tryptase inhibitor with a suitable pharmacokinetic profile for further clinical evaluation. PubMed: 22192588DOI: 10.1016/J.BMCL.2011.11.119 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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