5K1V
Crystal structure of Endoplasmic Reticulum aminopeptidase 2 (ERAP2) in complex with a diaminobenzoic acid derivative ligand.
Summary for 5K1V
| Entry DOI | 10.2210/pdb5k1v/pdb |
| Descriptor | Endoplasmic reticulum aminopeptidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | endoplasmic reticulum aminopeptidase, hydrolase, zinc-binding metallopeptidase, diaminobenzoic acid derivative |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 228025.33 |
| Authors | Saridakis, E.,Papakyriakou, A.,Giastas, P.,Mpakali, A.,Mavridis, I.M.,Stratikos, E. (deposition date: 2016-05-18, release date: 2017-03-29, Last modification date: 2024-10-09) |
| Primary citation | Mpakali, A.,Giastas, P.,Deprez-Poulain, R.,Papakyriakou, A.,Koumantou, D.,Gealageas, R.,Tsoukalidou, S.,Vourloumis, D.,Mavridis, I.M.,Stratikos, E.,Saridakis, E. Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency. ACS Med Chem Lett, 8:333-337, 2017 Cited by PubMed Abstract: Endoplasmic reticulum aminopeptidase 2 assists with the generation of antigenic peptides for presentation onto Major Histocompatibility Class I molecules in humans. Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive immune responses. To better understand the structural elements of inhibitors that govern their binding affinity to the ERAP2 active site, we cocrystallized ERAP2 with a medium activity 3,4-diaminobenzoic acid inhibitor and a poorly active hydroxamic acid derivative. Comparison of these two crystal structures with a previously solved structure of ERAP2 in complex with a potent phosphinic pseudopeptide inhibitor suggests that engaging the substrate N-terminus recognition properties of the active site is crucial for inhibitor binding even in the absence of a potent zinc-binding group. Proper utilization of all five major pharmacophores is necessary, however, to optimize inhibitor potency. PubMed: 28337326DOI: 10.1021/acsmedchemlett.6b00505 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.897 Å) |
Structure validation
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