The First Structure of Dipeptidyl-peptidase III Provides Insight into the Catalytic Mechanism and Mode of Substrate Binding
| Autor: | Nina Jajčanin-Jozić, Pravas Kumar Baral, Karl Gruber, Peter Macheroux, Sigrid Deller, Marija Abramić |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular metabolism [Dipeptidyl-Peptidases and Tripeptidyl-Peptidases] Stereochemistry chemistry [Dipeptidyl-Peptidases and Tripeptidyl-Peptidases] Peptide Saccharomyces cerevisiae Biochemistry Catalysis 03 medical and health sciences 0302 clinical medicine Thermolysin ddc:570 Cleave Hydrolase dipeptidyl-peptidase III crystal structure metallopeptidase thermolysin neprilysin Binding site Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites dipeptidyl peptidase III enzymology [Saccharomyces cerevisiae] Cell Biology metabolism [Zinc] Protein Structure Tertiary 3. Good health Amino acid N-terminus Zinc Enzyme chemistry 030220 oncology & carcinogenesis Protein Binding |
| Zdroj: | The journal of biological chemistry 283, 22316-22324 (2008). doi:10.1074/jbc.M803522200 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m803522200 |
| Popis: | Dipeptidyl-peptidases III (DPP III) are zinc-dependent enzymes that specifically cleave the first two amino acids from the N terminus of different length peptides. In mammals, DPP III is associated with important physiological functions and is a potential biomarker for certain types of cancer. Here, we present the 1.95-Å ; crystal structure of yeast DPP III representing the prototype for the M49 family of metallopeptidases. It shows a novel fold with two domains forming a wide cleft containing the catalytic metal ion. DPP III exhibits no overall similarity to other metallopeptidases, such as thermolysin and neprilysin, but zinc coordination and catalytically important residues are structurally conserved. Substrate recognition is accomplished by a binding site for the N terminus of the peptide at an appropriate distance from the metal center and by a series of conserved arginine residues anchoring the C termini of different length substrates. |
| Databáze: | OpenAIRE |
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