7O50
Crystal structure of human legumain in complex with Gly-Ser-Asn peptide
Summary for 7O50
| Entry DOI | 10.2210/pdb7o50/pdb |
| Descriptor | Legumain, GLY-SER-ASN, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | enzyme, cysteine protease, ligase, asparaginyl endopeptidase, substrate, hydrolase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 62209.35 |
| Authors | Dall, E.,Brandstetter, H. (deposition date: 2021-04-07, release date: 2021-09-22, Last modification date: 2024-10-16) |
| Primary citation | Dall, E.,Stanojlovic, V.,Demir, F.,Briza, P.,Dahms, S.O.,Huesgen, P.F.,Cabrele, C.,Brandstetter, H. The Peptide Ligase Activity of Human Legumain Depends on Fold Stabilization and Balanced Substrate Affinities. Acs Catalysis, 11:11885-11896, 2021 Cited by PubMed Abstract: 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. PubMed: 34621593DOI: 10.1021/acscatal.1c02057 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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