5obt

Fully activated A. thaliana legumain isoform gamma in complex with Ac-YVAD-CMK

spinqualitylabelsall models 5obt, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5obt is a 6 chain structure with sequence from Arabidopsis thaliana and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: 0QE, ACE, SNN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VPEG_ARATH Asparagine-specific endopeptidase involved in the processing of vacuolar seed protein precursors into the mature forms (PubMed:10417725). Probably involved in post-translational proteolysis of seed storage proteins in the protein storage vacuole of developing seeds (PubMed:14688293). Publication Abstract from PubMed Legumain is a dual-function protease peptide ligase whose activities are of great interest to researchers studying plant physiology and to biotechnological applications. However, the molecular mechanisms determining the specificities for proteolysis and ligation are unclear because structural information on the substrate recognition by a fully activated plant legumain is unavailable. Here, we present the X-ray structure of Arabidopsis thaliana legumain isoform gamma (AtLEGgamma) in complex with the covalent peptidic Ac-YVAD chloro methyl ketone (CMK) inhibitor targeting the catalytic cysteine. Mapping of the specificity pockets preceding the substrate cleavage site explained the known substrate preference. The comparison of inhibited and free AtLEGgamma structures disclosed a substrate-induced disorder-order transition with synergistic rearrangements in the substrate recognition sites. Docking and in vitro studies with an AtLEGgamma ligase substrate, sunflower trypsin inhibitor (SFTI), revealed a canonical, protease substrate-like binding to the active site binding pockets preceding and following the cleavage site. We found the interaction of the second residue after the scissile bond, P2'-S2', to be critical for deciding on proteolysis versus cyclization. cis-trans-Isomerization of the cyclic peptide product triggered its release from the AtLEGgamma active site and prevented inadvertent cleavage. The presented integrative mechanisms of proteolysis and ligation (transpeptidation) explain the interdependence of legumain and its preferred substrates and provide a rational framework for engineering optimized proteases, ligases, and substrates. Structural analyses of Arabidopsis thaliana legumain gamma reveal the differential recognition and processing of proteolysis and ligation substrates.,Zauner FB, Elsasser B, Dall E, Cabrele C, Brandstetter H J Biol Chem. 2018 Apr 8. pii: M117.817031. doi: 10.1074/jbc.M117.817031. PMID:29628443 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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