1LTO

Human alpha1-tryptase

Summary for 1LTO

• Entry DOI: 10.2210/pdb1lto/pdb
• Descriptor: alpha tryptase I (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 110931.02

Authors

Marquardt, U.,Zettl, F.,Huber, R.,Bode, W.,Sommerhoff, C.P. (deposition date: 2002-05-20, release date: 2003-05-20, Last modification date: 2024-10-09)

Primary citation

Marquardt, U.,Zettl, F.,Huber, R.,Bode, W.,Sommerhoff, C.P.
The Crystal Structure of Human alpha1-Tryptase Reveals a Blocked Substrate-binding Region
J.MOL.BIOL., 321:491-502, 2002

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.

PubMed: 12162961
DOI: 10.1016/S0022-2836(02)00625-3

Experimental method

X-RAY DIFFRACTION (2.2 Å)