The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region.
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Marquardt U, Zettl F, Huber R, Bode W, Sommerhoff C
The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region.
J Mol Biol. 2002 Aug 16;321(3):491-502.
- PubMed ID
- 12162961 [ View in PubMed]
- Abstract
Human mast cell tryptases represent a subfamily of trypsin-like serine proteinases implicated in asthma. Unlike beta-tryptases, alpha-tryptases apparently are proteolytically inactive. We have solved the 2.2A crystal structure of mature human alpha1-tryptase. It reveals a frame-like tetrameric architecture that, surprisingly, does not require heparin-binding for stability. In marked contrast to beta2-tryptase, the Ser214-Gly219 segment, which normally provides the template for substrate binding, is kinked in alpha-tryptase, thereby blocking its non-primed subsites. This so far unobserved subsite distortion is incompatible with productive substrate binding and processing. alpha-Tryptase apparently is trapped in this off-conformation by repulsions and attractions of the Asp216 side-chain. However, proteolytic activity could be generated by an induced-fit mechanism.