1FQ3

CRYSTAL STRUCTURE OF HUMAN GRANZYME B

Summary for 1FQ3

• Entry DOI: 10.2210/pdb1fq3/pdb
• Descriptor: GRANZYME B, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION (3 entities in total)
• Functional Keywords: chymotrypsin-like serine proteinase, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasmic granule: P10144
• Total number of polymer chains: 2
• Total formula weight: 52472.29

Authors

Estebanez-Perpina, E.,Fuentes-Prior, P.,Belorgey, D.,Rubin, H.,Bode, W. (deposition date: 2000-09-03, release date: 2001-01-31, Last modification date: 2024-10-16)

Primary citation

Estebanez-Perpina, E.,Fuentes-Prior, P.,Belorgey, D.,Braun, M.,Kiefersauer, R.,Maskos, K.,Huber, R.,Rubin, H.,Bode, W.
Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
Biol.Chem., 381:1203-1214, 2000

PubMed Abstract: 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.

PubMed: 11209755
DOI: 10.1515/BC.2000.148

Experimental method

X-RAY DIFFRACTION (3.1 Å)