1orf

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Revision as of 16:29, 12 November 2007

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spinqualitylabelsall models 1orf, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The Oligomeric Structure of Human Granzyme A Reveals the Molecular Determinants of Substrate Specificity

Overview

The cell death-inducing serine protease granzyme A (GzmA) has a unique, disulfide-linked quaternary structure. The structure of human GzmA bound, to a tripeptide CMK inhibitor, determined at a resolution of 2.4 A, reveals that the oligomeric state contributes to substrate selection by, limiting access to the active site for potential macromolecular substrates, and inhibitors. Unlike other serine proteases, tetrapeptide substrate, preferences do not correlate well with natural substrate cleavage, sequences. This suggests that the context of the cleavage sequence within, a macromolecular substrate imposes another level of selection not observed, with the peptide substrates. Modeling of inhibitors bound to the GzmA, active site shows that the dimer also contributes to substrate specificity, in a unique manner by extending the active-site cleft. The crystal, structure, along with substrate library profiling and mutagenesis, has, allowed us to identify and rationally manipulate key components involved, in GzmA substrate specificity.

About this Structure

1ORF is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Active as Granzyme A, with EC number 3.4.21.78 Full crystallographic information is available from OCA.

Reference

The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity., Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS, Nat Struct Biol. 2003 Jul;10(7):527-34. PMID:12819769

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