4MSL
Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with AF40431
Summary for 4MSL
| Entry DOI | 10.2210/pdb4msl/pdb |
| Related | 3F6K |
| Descriptor | Sortilin, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | prongf, alzheimer's disease, beta-propeller, asp-box repeat, vps10p domain, 10cc domain, receptor sorting, peptide binding, protein binding, membrane, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 79639.68 |
| Authors | Andersen, J.L.,Strandbygaard, D.,Thirup, S. (deposition date: 2013-09-18, release date: 2014-02-12, Last modification date: 2024-11-27) |
| Primary citation | Andersen, J.L.,Schrder, T.J.,Christensen, S.,Strandbygard, D.,Pallesen, L.T.,Garcia-Alai, M.M.,Lindberg, S.,Langgard, M.,Eskildsen, J.C.,David, L.,Tagmose, L.,Simonsen, K.B.,Maltas, P.J.,Rnn, L.C.,de Jong, I.E.,Malik, I.J.,Egebjerg, J.,Karlsson, J.J.,Uppalanchi, S.,Sakumudi, D.R.,Eradi, P.,Watson, S.P.,Thirup, S. Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor-ligand complex. Acta Crystallogr.,Sect.D, 70:451-460, 2014 Cited by PubMed Abstract: Sortilin is a type I membrane glycoprotein belonging to the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors and is most abundantly expressed in the central nervous system. Sortilin has emerged as a key player in the regulation of neuronal viability and has been implicated as a possible therapeutic target in a range of disorders. Here, the identification of AF40431, the first reported small-molecule ligand of sortilin, is reported. Crystals of the sortilin-AF40431 complex were obtained by co-crystallization and the structure of the complex was solved to 2.7 Å resolution. AF40431 is bound in the neurotensin-binding site of sortilin, with the leucine moiety of AF40431 mimicking the binding mode of the C-terminal leucine of neurotensin and the 4-methylumbelliferone moiety of AF40431 forming π-stacking with a phenylalanine. PubMed: 24531479DOI: 10.1107/S1399004713030149 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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