1A0L

HUMAN BETA-TRYPTASE: A RING-LIKE TETRAMER WITH ACTIVE SITES FACING A CENTRAL PORE

Summary for 1A0L

• Entry DOI: 10.2210/pdb1a0l/pdb
• Descriptor: BETA-TRYPTASE, (2S)-3-(4-carbamimidoylphenyl)-2-hydroxypropanoic acid (3 entities in total)
• Functional Keywords: trypsin-like serine proteinase, tetramer, heparin, allergy, asthma, serine proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P20231
• Total number of polymer chains: 4
• Total formula weight: 110410.10

Authors

Pereira, P.J.B.,Bergner, A.,Macedo-Ribeiro, S.,Huber, R.,Matschiner, G.,Fritz, H.,Sommerhoff, C.P.,Bode, W. (deposition date: 1997-12-03, release date: 1999-03-23, Last modification date: 2024-10-30)

Primary citation

Pereira, P.J.,Bergner, A.,Macedo-Ribeiro, S.,Huber, R.,Matschiner, G.,Fritz, H.,Sommerhoff, C.P.,Bode, W.
Human beta-tryptase is a ring-like tetramer with active sites facing a central pore.
Nature, 392:306-311, 1998

PubMed Abstract: Human tryptase, a mast-cell-specific serine proteinase that may be involved in causing asthma and other allergic and inflammatory disorders, is unique in two respects: it is enzymatically active only as a heparin-stabilized tetramer, and it is resistant to all known endogenous proteinase inhibitors. The 3-A crystal structure of human beta-tryptase in a complex with 4-amidinophenyl pyruvic acid shows four quasi-equivalent monomers arranged in a square flat ring of pseudo 222 symmetry. Each monomer contacts its neighbours at two different interfaces through six loop segments. These loops are located around the active site of beta-tryptase and differ considerably in length and conformation from loops of other trypsin-like proteinases. The four active centres of the tetramer are directed towards an oval central pore, restricting access for macromolecular substrates and enzyme inhibitors. Heparin chains might stabilize the complex by binding to an elongated patch of positively charged residues spanning two adjacent monomers. The nature of this unique tetrameric architecture explains many of tryptase's biochemical properties and provides a basis for the rational design of monofunctional and bifunctional tryptase inhibitors.

PubMed: 9521329
DOI: 10.1038/32703

Experimental method

X-RAY DIFFRACTION (3 Å)