RAT GRANZYME B [N66Q] COMPLEXED TO ECOTIN [81-84 IEPD]RAT GRANZYME B [N66Q] COMPLEXED TO ECOTIN [81-84 IEPD]

Structural highlights

1fi8 is a 6 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895 and Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GRAB_RAT] This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Asp. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes mediating apoptosis (By similarity). [ECOT_ECOLI] General inhibitor of pancreatic serine proteases: inhibits chymotrypsin, trypsin, elastases, factor X, kallikrein as well as a variety of other proteases. The strength of inhibition does not appear to be correlated with a particular protease specificity.[HAMAP-Rule:MF_00706]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Granzyme B is a serine protease of the chymotrypsin fold that mediates cell death by cytotoxic lymphocytes. It is a processing enzyme, requiring extended peptide substrates containing an Asp residue. The determinants that allow for this substrate specificity are revealed in the three-dimensional structure of granzyme B in complex with a macromolecular inhibitor. The primary specificity for Asp occurs through a side-on interaction with Arg 226, a buried Arg side chain of granzyme B. An additional nine amino acids make contact with the substrate and define the granzyme B extended substrate specificity profile. The substrate determinants found in this structure are shared by other members of this protein class and help to reveal the properties that define substrate specificity.

The structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity.,Waugh SM, Harris JL, Fletterick R, Craik CS Nat Struct Biol. 2000 Sep;7(9):762-5. PMID:10966646[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Waugh SM, Harris JL, Fletterick R, Craik CS. The structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity. Nat Struct Biol. 2000 Sep;7(9):762-5. PMID:10966646 doi:10.1038/78992

1fi8, resolution 2.20Å

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