3KGQ
Carboxypeptidase A liganded to an organic small-molecule: conformational changes
Summary for 3KGQ
| Entry DOI | 10.2210/pdb3kgq/pdb |
| Descriptor | Carboxypeptidase A1, ZINC ION, SODIUM ION, ... (8 entities in total) |
| Functional Keywords | intestinal protease, zinc-metallocarboxypeptidase-citrate ternary complex, carboxypeptidase, hydrolase, metal-binding, metalloprotease |
| Biological source | Bos taurus (bovine) |
| Cellular location | Secreted, extracellular space: P00730 |
| Total number of polymer chains | 1 |
| Total formula weight | 35823.05 |
| Authors | Fernandez, D.,Boix, E.,Pallares, I.,Aviles, F.X.,Vendrell, J. (deposition date: 2009-10-29, release date: 2010-10-27, Last modification date: 2024-11-13) |
| Primary citation | Fernandez, D.,Boix, E.,Pallares, I.,Aviles, F.X.,Vendrell, J. Structural and Functional Analysis of the Complex between Citrate and the Zinc Peptidase Carboxypeptidase A Enzyme Res, 2011:128676-128676, 2011 Cited by PubMed Abstract: A high-resolution carboxypeptidase-Zn(2+)-citrate complex was studied by X-ray diffraction and enzyme kinetics for the first time. The citrate molecule acts as a competitive inhibitor of this benchmark zinc-dependent peptidase, chelating the catalytic zinc ion in the active site of the enzyme and inducing a conformational change such that carboxypeptidase adopts the conformation expected to occur by substrate binding. Citrate adopts an extended conformation with half of the molecule facing the zinc ion, while the other half is docked in the S1' hydrophobic specificity pocket of the enzyme, in contrast with the binding mode expected for a substrate like phenylalanine or a peptidomimetic inhibitor like benzylsuccinic acid. Combined structural and enzymatic analysis describes the characteristics of the binding of this ligand that, acting against physiologically relevant zinc-dependent proteases, may serve as a general model in the design of new drug-protecting molecules for the oral delivery of drugs of peptide origin. PubMed: 21804935DOI: 10.4061/2011/128676 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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