3GY4
A comparative study on the inhibition of bovine beta-trypsin by bis-benzamidines diminazene and pentamidine by X-ray crystallography and ITC
Summary for 3GY4
| Entry DOI | 10.2210/pdb3gy4/pdb |
| Related | 3GY2 3GY3 3GY5 3GY6 3GY7 3GY8 |
| Descriptor | Cationic trypsin, CALCIUM ION, P-AMINO BENZAMIDINE, ... (6 entities in total) |
| Functional Keywords | bovine beta-trypsin, p-amino benzamidine, protein-ligand complex, protein-ligand interaction, calcium, digestion, disulfide bond, hydrolase, metal-binding, protease, secreted, serine protease, zymogen |
| Biological source | Bos taurus (bovine,cow) |
| Cellular location | Secreted, extracellular space: P00760 |
| Total number of polymer chains | 1 |
| Total formula weight | 24387.26 |
| Authors | Perilo, C.S.,Pereira, M.T.,Santoro, M.M.,Nagem, R.A.P. (deposition date: 2009-04-03, release date: 2010-03-23, Last modification date: 2011-07-13) |
| Primary citation | Perilo, C.S.,Pereira, M.T.,Santoro, M.M.,Nagem, R.A. Structural binding evidence of the trypanocidal drugs Berenil and Pentacarinate active principles to a serine protease model. Int.J.Biol.Macromol., 46:502-511, 2010 Cited by PubMed Abstract: Bovine trypsin is a model system for the serine protease class of enzymes, which is an important target for contemporary medicinal chemistry. Some structural and thermodynamic reports are available on its interaction with benzamidine-based compounds but no structural information is available so far on its binding modes to the active principles of the trypanocidal drugs Pentacarinate (pentamidine) and Berenil (diminazene). The crystallographic structures of bovine beta-trypsin in complex with the ligands were determined to a resolution of 1.57 A (diminazene) and 1.70 A (diminazene and pentamidine). The second benzamidine moieties in these inhibitors are bound to the enzyme in different hot spots and only few hydrogen bonds mediate these interactions. Thermodynamic parameters for the association of pentamidine with beta-trypsin reveal that this inhibitor has about 1.3-fold lower affinity than diminazene. Moreover its binding mode resembles other benzamidine-based compounds that assess the aryl binding pocket of the enzyme; however, with almost 2.5-fold higher affinity. This is the first structural evidence of the binding of Berenil and Pentacarinate active principles trypanocidal drugs to serine proteases. PubMed: 20356563DOI: 10.1016/j.ijbiomac.2010.03.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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