5LA7
Crystal structure of human proheparanase, in complex with glucuronic acid configured aziridine probe JJB355
Summary for 5LA7
| Entry DOI | 10.2210/pdb5la7/pdb |
| Descriptor | Heparanase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | hydrolase, heparanase, proenzyme, gh79 |
| Biological source | Homo sapiens (Human) |
| Cellular location | Lysosome membrane; Peripheral membrane protein: Q9Y251 |
| Total number of polymer chains | 1 |
| Total formula weight | 59692.09 |
| Authors | Wu, L.,Jin, Y.,Davies, G.J. (deposition date: 2016-06-13, release date: 2017-05-31, Last modification date: 2024-11-06) |
| Primary citation | Wu, L.,Jiang, J.,Jin, Y.,Kallemeijn, W.W.,Kuo, C.L.,Artola, M.,Dai, W.,van Elk, C.,van Eijk, M.,van der Marel, G.A.,Codee, J.D.C.,Florea, B.I.,Aerts, J.M.F.G.,Overkleeft, H.S.,Davies, G.J. Activity-based probes for functional interrogation of retaining beta-glucuronidases. Nat. Chem. Biol., 13:867-873, 2017 Cited by PubMed Abstract: Humans express at least two distinct β-glucuronidase enzymes that are involved in disease: exo-acting β-glucuronidase (GUSB), whose deficiency gives rise to mucopolysaccharidosis type VII, and endo-acting heparanase (HPSE), whose overexpression is implicated in inflammation and cancers. The medical importance of these enzymes necessitates reliable methods to assay their activities in tissues. Herein, we present a set of β-glucuronidase-specific activity-based probes (ABPs) that allow rapid and quantitative visualization of GUSB and HPSE in biological samples, providing a powerful tool for dissecting their activities in normal and disease states. Unexpectedly, we find that the supposedly inactive HPSE proenzyme proHPSE is also labeled by our ABPs, leading to surprising insights regarding structural relationships between proHPSE, mature HPSE, and their bacterial homologs. Our results demonstrate the application of β-glucuronidase ABPs in tracking pathologically relevant enzymes and provide a case study of how ABP-driven approaches can lead to discovery of unanticipated structural and biochemical functionality. PubMed: 28581485DOI: 10.1038/nchembio.2395 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.94 Å) |
Structure validation
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