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http://purl.uniprot.org/citations/9384562http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9384562http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9384562http://www.w3.org/2000/01/rdf-schema#comment"

Background

Tryptase is a trypsin-like serine proteinase stored in the cytoplasmic granules of mast cells, which has been implicated in a number of mast cell related disorders such as asthma and rheumatoid arthritis. Unlike almost all other serine proteinases, tryptase is fully active in plasma and in the extracellular space, as there are no known natural inhibitors of tryptase in humans. Leech-derived tryptase inhibitor (LDTI), a protein of 46 amino acids, is the first molecule found to bind tightly to and specifically inhibit human tryptase in the nanomolar range. LDTI also inhibits trypsin and chymotrypsin with similar affinities. The structure of LDTI in complex with an inhibited proteinase could be used as a template for the development of low molecular weight tryptase inhibitors.

Results

The crystal structure of the complex between trypsin and LDTI was solved at 2.0 A resolution and a model of the LDTI-tryptase complex was created, based on this X-ray structure. LDTI has a very similar fold to the third domain of the turkey ovomucoid inhibitor. LDTI interacts with trypsin almost exclusively through its binding loop (residues 3-10) and especially through the sidechain of the specificity residue Lys8. Our modeling studies indicate that these interactions are maintained in the LDTI-tryptase complex.

Conclusions

The insertion of nine residues after residue 174 in tryptase, relative to trypsin and chymotrypsin, prevents inhibition by other trypsin inhibitors and is certainly responsible for the higher specificity of tryptase relative to trypsin. In LDTI, the disulfide bond between residues 4 and 25 causes a sharp turn from the binding loop towards the N terminus, holding the N terminus away from the 174 loop of tryptase."xsd:string
http://purl.uniprot.org/citations/9384562http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(97)00296-7"xsd:string
http://purl.uniprot.org/citations/9384562http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(97)00296-7"xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/author"Priestle J.P."xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/author"Priestle J.P."xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/author"di Marco S."xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/author"di Marco S."xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/date"1997"xsd:gYear
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/date"1997"xsd:gYear
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/pages"1465-1474"xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/pages"1465-1474"xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/title"Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI-tryptase system."xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/title"Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI-tryptase system."xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/9384562http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/9384562http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9384562
http://purl.uniprot.org/citations/9384562http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9384562
http://purl.uniprot.org/citations/9384562http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/9384562
http://purl.uniprot.org/citations/9384562http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/9384562
http://purl.uniprot.org/uniprot/P80424http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/9384562
http://purl.uniprot.org/uniprot/P00761http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/9384562
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