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| {{STRUCTURE_1tkr| PDB=1tkr | SCENE= }} | | {{STRUCTURE_1tkr| PDB=1tkr | SCENE= }} |
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| '''Human Dipeptidyl Peptidase IV/CD26 inhibited with Diisopropyl FluoroPhosphate'''
| | ===Human Dipeptidyl Peptidase IV/CD26 inhibited with Diisopropyl FluoroPhosphate=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15175333}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15175333 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15175333}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Beta-propeller]] | | [[Category: Beta-propeller]] |
| [[Category: Homodimer]] | | [[Category: Homodimer]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:04:18 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:15:35 2008'' |
