Summary for 1U8E
| Entry DOI | 10.2210/pdb1u8e/pdb |
| Related | 1TK3 1TKR |
| Descriptor | Dipeptidyl peptidase IV, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total) |
| Functional Keywords | alpha/beta hydrolase, beta-propeller, homodimer, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 175150.11 |
| Authors | Bjelke, J.R.,Christensen, J.,Branner, S.,Wagtmann, N.,Olsen, C.,Kanstrup, A.B.,Rasmussen, H.B. (deposition date: 2004-08-05, release date: 2004-08-17, Last modification date: 2024-10-30) |
| Primary citation | BJELKE, J.R.,CHRISTENSEN, J.,BRANNER, S.,WAGTMANN, N.,OLSEN, C.,KANSTRUP, A.B.,RASMUSSEN, H.B. Tyrosine 547 constitutes an essential part of the catalytic mechanism of dipeptidyl peptidase IV J.Biol.Chem., 279:34691-34697, 2004 Cited by PubMed Abstract: Human dipeptidyl peptidase IV (DPP-IV) is a ubiquitously expressed type II transmembrane serine protease. It cleaves the penultimate positioned prolyl bonds at the N terminus of physiologically important peptides such as the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic peptide. In this study, we have characterized different active site mutants. The Y547F mutant as well as the catalytic triad mutants S630A, D708A, and H740L showed less than 1% wild type activity. X-ray crystal structure analysis of the Y547F mutant revealed no overall changes compared with wild type apoDPP-IV, except the ablation of the hydroxyl group of Tyr(547) and a water molecule positioned in close proximity to Tyr(547). To elucidate further the reaction mechanism, we determined the crystal structure of DPP-IV in complex with diisopropyl fluorophosphate, mimicking the tetrahedral intermediate. The kinetic and structural findings of the tyrosine residue are discussed in relation to the catalytic mechanism of DPP-IV and to the inhibitory mechanism of the 2-cyanopyrrolidine class of potent DPP-IV inhibitors, proposing an explanation for the specificity of this class of inhibitors for the S9b family among serine proteases. PubMed: 15175333DOI: 10.1074/jbc.M405400200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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