4a6l
From Proteopedia
beta-tryptase inhibitor
Structural highlights
Function[TRYB1_HUMAN] Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity). Publication Abstract from PubMedA 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 beta-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 beta-tryptase inhibitor with a suitable pharmacokinetic profile for further clinical evaluation. Structure-based library design and the discovery of a potent and selective mast cell beta-tryptase inhibitor as an oral therapeutic agent.,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 HW Bioorg Med Chem Lett. 2012 Jan 15;22(2):1049-54. Epub 2011 Dec 7. PMID:22192588[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Tryptase | Maignan, S | Mathieu, M | Hydrolase | Inhibitor
