1an1
From Proteopedia
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LEECH-DERIVED TRYPTASE INHIBITOR/TRYPSIN COMPLEX
Overview
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.
About this Structure
1AN1 is a Protein complex structure of sequences from Hirudo medicinalis and Sus scrofa with CA as ligand. Active as Trypsin, with EC number 3.4.21.4 Structure known Active Sites: CA and P1. 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 Nov 5 15:49:40 2007
