3UNQ
Bovine trypsin variant X(triplePhe227) in complex with small molecule inhibitor
Summary for 3UNQ
| Entry DOI | 10.2210/pdb3unq/pdb |
| Related | 1V2K 3UNP 3UNS 3UPE 3UQO 3UQV 3UQZ |
| Descriptor | Cationic trypsin, CALCIUM ION, BENZAMIDINE, ... (8 entities in total) |
| Functional Keywords | trypsin-like serine protease, hydrolase, protein binding, duodenum, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Bos taurus (bovine) |
| Total number of polymer chains | 1 |
| Total formula weight | 24221.23 |
| Authors | Tziridis, A.,Neumann, P.,Kolenko, P.,Stubbs, M.T. (deposition date: 2011-11-16, release date: 2012-11-21, Last modification date: 2024-10-30) |
| Primary citation | Tziridis, A.,Rauh, D.,Neumann, P.,Kolenko, P.,Menzel, A.,Brauer, U.,Ursel, C.,Steinmetzer, P.,Sturzebecher, J.,Schweinitz, A.,Steinmetzer, T.,Stubbs, M.T. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues. Biol.Chem., 395:891-903, 2014 Cited by PubMed Abstract: A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine proteinase inhibitors with trypsin variants onto which the ligand-binding site of factor Xa has been grafted. Despite conservative mutations of only two residues not immediately in contact with ligands (second shell residues), significant differences in the affinity profiles of the variants are observed. Structural analyses demonstrate that these are due to multiple effects, including differences in the structure of the binding site, differences in target flexibility and differences in inhibitor binding modes. The data presented here highlight the myriad competing microscopic processes that contribute to protein-ligand interactions and emphasize the difficulties in predicting affinity from structure. PubMed: 25003390DOI: 10.1515/hsz-2014-0158 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.62 Å) |
Structure validation
Download full validation report
