1MX1
Crystal Structure of Human Liver Carboxylesterase in complex with tacrine
Summary for 1MX1
| Entry DOI | 10.2210/pdb1mx1/pdb |
| Related | 1MX5 1MX9 |
| Descriptor | liver Carboxylesterase I, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | esterase, hydrolase, esterase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 6 |
| Total formula weight | 367246.28 |
| Authors | Bencharit, S.,Morton, C.L.,Hyatt, J.L.,Kuhn, P.,Danks, M.K.,Potter, P.M.,Redinbo, M.R. (deposition date: 2002-10-01, release date: 2003-04-22, Last modification date: 2024-12-25) |
| Primary citation | Bencharit, S.,Morton, C.L.,Hyatt, J.L.,Kuhn, P.,Danks, M.K.,Potter, P.M.,Redinbo, M.R. Crystal Structure of Human Carboxylesterase 1 Complexed with the Alzheimer's Drug Tacrine: From Binding Promiscuity to Selective Inhibition CHEM.BIOL., 10:341-349, 2003 Cited by PubMed Abstract: Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that plays important roles in narcotic metabolism, clinical prodrug activation, and the processing of fatty acid and cholesterol derivatives. We determined the 2.4 A crystal structure of hCE1 in complex with tacrine, the first drug approved for treating Alzheimer's disease, and compare this structure to the Torpedo californica acetylcholinesterase (AcChE)-tacrine complex. Tacrine binds in multiple orientations within the catalytic gorge of hCE1, while it stacks in the smaller AcChE active site between aromatic side chains. Our results show that hCE1's promiscuous action on distinct substrates is enhanced by its ability to interact with ligands in multiple orientations at once. Further, we use our structure to identify tacrine derivatives that act as low-micromolar inhibitors of hCE1 and may provide new avenues for treating narcotic abuse and cholesterol-related diseases. PubMed: 12725862DOI: 10.1016/S1074-5521(03)00071-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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