3CWM
Crystal structure of alpha-1-antitrypsin complexed with citrate
Summary for 3CWM
| Entry DOI | 10.2210/pdb3cwm/pdb |
| Related | 3CWL |
| Descriptor | Alpha-1-antitrypsin, CITRIC ACID (3 entities in total) |
| Functional Keywords | antitrypsin, polymerisation, protein aggregation, protein unfolding, serpin, acute phase, disease mutation, glycoprotein, protease inhbitor, secreted, serine protease inhibitor, blood coagulation, protease inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Secreted. Short peptide from AAT: Secreted, extracellular space, extracellular matrix: P01009 |
| Total number of polymer chains | 1 |
| Total formula weight | 44602.48 |
| Authors | Morton, C.J.,Hansen, G.,Feil, S.C.,Adams, J.J.,Parker, M.W. (deposition date: 2008-04-22, release date: 2008-09-23, Last modification date: 2024-10-30) |
| Primary citation | Pearce, M.C.,Morton, C.J.,Feil, S.C.,Hansen, G.,Adams, J.J.,Parker, M.W.,Bottomley, S.P. Preventing serpin aggregation: The molecular mechanism of citrate action upon antitrypsin unfolding. Protein Sci., 17:2127-2133, 2008 Cited by PubMed Abstract: The aggregation of antitrypsin into polymers is one of the causes of neonatal hepatitis, cirrhosis, and emphysema. A similar reaction resulting in disease can occur in other human serpins, and collectively they are known as the serpinopathies. One possible therapeutic strategy involves inhibiting the conformational changes involved in antitrypsin aggregation. The citrate ion has previously been shown to prevent antitrypsin aggregation and maintain the protein in an active conformation; its mechanism of action, however, is unknown. Here we demonstrate that the citrate ion prevents the initial misfolding of the native state to a polymerogenic intermediate in a concentration-dependent manner. Furthermore, we have solved the crystal structure of citrate bound to antitrypsin and show that a single citrate molecule binds in a pocket between the A and B beta-sheets, a region known to be important in maintaining antitrypsin stability. PubMed: 18780818DOI: 10.1110/ps.037234.108 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.51 Å) |
Structure validation
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