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| - | [[Image:1an1.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1an1.png|left|200px]] |
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| | {{STRUCTURE_1an1| PDB=1an1 | SCENE= }} | | {{STRUCTURE_1an1| PDB=1an1 | SCENE= }} |
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| - | '''LEECH-DERIVED TRYPTASE INHIBITOR/TRYPSIN COMPLEX'''
| + | ===LEECH-DERIVED TRYPTASE INHIBITOR/TRYPSIN COMPLEX=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9384562}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9384562 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9384562}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Serine proteinase inhibitor]] | | [[Category: Serine proteinase inhibitor]] |
| | [[Category: Tryptase inhibition]] | | [[Category: Tryptase inhibition]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:28:15 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 17:11:50 2008'' |
Revision as of 14:11, 30 June 2008
Template:STRUCTURE 1an1
LEECH-DERIVED TRYPTASE INHIBITOR/TRYPSIN COMPLEX
Template:ABSTRACT PUBMED 9384562
About this Structure
1AN1 is a Protein complex structure of sequences from Hirudo medicinalis and Sus scrofa. Full crystallographic information is available from OCA.
Reference
Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI-tryptase system., Di Marco S, Priestle JP, Structure. 1997 Nov 15;5(11):1465-74. PMID:9384562
Page seeded by OCA on Mon Jun 30 17:11:50 2008
