5LLS
Porcine dipeptidyl peptidase IV in complex with 8-(3-aminopiperidin-1-yl)-7-[(2-bromophenyl)methyl]-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
Summary for 5LLS
| Entry DOI | 10.2210/pdb5lls/pdb |
| Descriptor | Dipeptidyl peptidase 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | peptidase, inhibitor, complex, hydrolase |
| Biological source | Sus scrofa (Pig) |
| Total number of polymer chains | 4 |
| Total formula weight | 364428.55 |
| Authors | Nar, H.,Blaesse, M. (deposition date: 2016-07-28, release date: 2016-09-14, Last modification date: 2024-10-23) |
| Primary citation | Schnapp, G.,Klein, T.,Hoevels, Y.,Bakker, R.A.,Nar, H. Comparative Analysis of Binding Kinetics and Thermodynamics of Dipeptidyl Peptidase-4 Inhibitors and Their Relationship to Structure. J.Med.Chem., 59:7466-7477, 2016 Cited by PubMed Abstract: The binding kinetics and thermodynamics of dipeptidyl peptidase (DPP)-4 inhibitors (gliptins) were investigated using surface plasmon resonance and isothermal titration calorimetry. Binding of gliptins to DPP-4 is a rapid electrostatically driven process. Off-rates were generally slow partly because of reversible covalent bond formation by some gliptins, and partly because of strong and extensive interactions. Binding of all gliptins is enthalpy-dominated due to strong ionic interactions and strong solvent-shielded hydrogen bonds. Using a congeneric series of molecules which represented the intermediates in the lead optimization program of linagliptin, the onset of slow binding kinetics and development of the thermodynamic repertoire were analyzed in the context of incremental changes of the chemical structures. All compounds rapidly associated, and therefore the optimization of affinity and residence time is highly correlated. The major contributor to the increasing free energy of binding was a strong increase of binding enthalpy, whereas entropic contributions remained low and constant despite significant addition of lipophilicity. PubMed: 27438064DOI: 10.1021/acs.jmedchem.6b00475 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.41 Å) |
Structure validation
Download full validation report
