Tryptase, a proteolytic enzyme,
is the predominant protein of human mast cells. Despite
significant sequence similarity to other trypsin-like
proteinases, tryptase possesses unique, as yet poorly
understood, properties. Most prominently, it is enzymatically
active only as a tetramer which requires the binding of
heparin for stabilization, and is resistant to all known
endogenous proteinase inhibitors. Together with other
preformed mediators (e.g., histamine and proteoglycans),
tryptase is stored in the secretory granules of mast cells
and is released in various allergic and certain inflammatory
disorders such as asthma, psoriasis, rheumatoid arthritis,
interstitial cystitis, and multiple sclerosis. Tryptase has
been implicated as a causal mediator of such disorders and
its involvement in the pathogenesis of asthma has recently
been supported by preliminary results of clinical trials with
the first synthetic tryptase inhibitors.
The team at the Max Planck Institute of Biochemistry (P.J.B.
Pereira, A. Bergner, S.
Macedo-Ribeiro, R. Huber and W. Bode) has now determined the
crystal structure of human beta-tryptase provided by G.
Matschiner, H. Fritz and C.P. Sommerhoff at the Department of
Clinical Chemistry and
Clinical Biochemistry at
the Ludwig Maximilian University, Muenchen.
The structure, published in a Letter to Nature (Human
beta-tryptase is a ring-like tetramer with active sites
facing a central pore, P.J.B. Pereira, A. Bergner, S.
Macedo-Ribeiro, R. Huber, G. Matschiner, H. Fritz, C.P.
Sommerhoff and W. Bode, Nature 392, 306) on March 19, 1998,
reveals four quasi-equivalent monomers arranged in a square
flat ring. Each monomer contacts its neighbours at two
differe
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Contact: Wolfram Bode
bode@biochem.mpg.de
+49-89-8578 2676
Max-Planck-Gesellschaft
25-Mar-1998