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Human beta-tryptase is a ring-like tetramer with active sites facing a central pore
- Source :
- Nature. 392(6673)
- Publication Year :
- 1998
-
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.
- Subjects :
- Models, Molecular
Serine Proteinase Inhibitors
Stereochemistry
Protein Conformation
Molecular Sequence Data
Tryptase
Crystallography, X-Ray
Serine
Structure-Activity Relationship
Protein structure
Chymases
Tetramer
Electrochemistry
Animals
Humans
Amino Acid Sequence
Mast Cells
Binding site
Lung
Multidisciplinary
Binding Sites
biology
Chemistry
Serine Endopeptidases
Rational design
Active site
biology.protein
Cattle
Tryptases
Subjects
Details
- ISSN :
- 00280836
- Volume :
- 392
- Issue :
- 6673
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....38c1d628f501dda73217f04c18298c57