1fq3
From Proteopedia
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'''CRYSTAL STRUCTURE OF HUMAN GRANZYME B''' | '''CRYSTAL STRUCTURE OF HUMAN GRANZYME B''' | ||
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[[Category: Rubin, H.]] | [[Category: Rubin, H.]] | ||
[[Category: Chymotrypsin-like serine proteinase]] | [[Category: Chymotrypsin-like serine proteinase]] | ||
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Revision as of 13:37, 2 May 2008
CRYSTAL STRUCTURE OF HUMAN GRANZYME B
Overview
Granzyme B is the prototypic member of the granzymes, a family of trypsin-like serine proteinases localized in the dense cytoplasmic granules of activated natural killer cells and cytotoxic T lymphocytes. Granzyme B directly triggers apoptosis in target cells by activating the caspase pathway, and has been implicated in the etiology of rheumatoid arthritis. Human granzyme B expressed in a baculovirus system has been crystallized without inhibitor and its structure has been determined to 3.1 A resolution, after considerably improving the diffraction power of the crystals by controlled humidity changes. The granzyme B structure reveals an overall fold similar to that found in cathepsin G and human chymase. The guanidinium group of Arg226, anchored at the back of the S1-specificity pocket, can form a salt bridge with the P1-Asp side chain of a bound peptide substrate. The architecture of the substrate binding site of granzyme B appears to be designed to accommodate and cleave hexapeptides such as the sequence Ile-Glu-Thr-Asp-/Ser-Gly present in the activation site of pro-caspase-3, a proven physiological substrate of granzyme B. These granzyme B crystals, with fully accessible active sites, are well suited for soaking with small synthetic inhibitors that might be used for a treatment of chronic inflammatory disorders.
About this Structure
1FQ3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue., Estebanez-Perpina E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W, Biol Chem. 2000 Dec;381(12):1203-14. PMID:11209755 Page seeded by OCA on Fri May 2 16:37:49 2008