7o50

Crystal structure of human legumain in complex with Gly-Ser-Asn peptide

spinqualitylabelsall models 7o50, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7o50 is a 4 chain structure with sequence from Homo sapiens 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 1.9Å Ligands: ACE, NAG, SNN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Protein modification by enzymatic breaking and forming of peptide bonds significantly expands the repertoire of genetically encoded protein sequences. The dual protease-ligase legumain exerts the two opposing activities within a single protein scaffold. Primarily localized to the endolysosomal system, legumain represents a key enzyme in the generation of antigenic peptides for subsequent presentation on the MHCII complex. Here we show that human legumain catalyzes the ligation and cyclization of linear peptides at near-neutral pH conditions, where legumain is intrinsically unstable. Conformational stabilization significantly enhanced legumain's ligase activity, which further benefited from engineering the prime substrate recognition sites for improved affinity. Additionally, we provide evidence that specific legumain activation states allow for differential regulation of its activities. Together these results set the basis for engineering legumain proteases and ligases with applications in biotechnology and drug development. The Peptide Ligase Activity of Human Legumain Depends on Fold Stabilization and Balanced Substrate Affinities.,Dall E, Stanojlovic V, Demir F, Briza P, Dahms SO, Huesgen PF, Cabrele C, Brandstetter H ACS Catal. 2021 Oct 1;11(19):11885-11896. doi: 10.1021/acscatal.1c02057. Epub , 2021 Sep 10. PMID:34621593 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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