1ORV
Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26)
Summary for 1ORV
| Entry DOI | 10.2210/pdb1orv/pdb |
| Descriptor | dipeptidyl peptidase IV, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | serine protease, oxyanion hole, substrate channeling, drug design, diabetes mellitus, hydrolase |
| Biological source | Sus scrofa (pig) |
| Total number of polymer chains | 4 |
| Total formula weight | 345563.39 |
| Authors | Engel, M.,Hoffmann, T.,Wagner, L.,Wermann, M.,Heiser, U.,Kiefersauer, R.,Huber, R.,Bode, W.,Demuth, H.U.,Brandstetter, H. (deposition date: 2003-03-16, release date: 2003-05-06, Last modification date: 2024-11-13) |
| Primary citation | Engel, M.,Hoffmann, T.,Wagner, L.,Wermann, M.,Heiser, U.,Kiefersauer, R.,Huber, R.,Bode, W.,Demuth, H.U.,Brandstetter, H. The Crystal Structure of Dipeptidyl Peptidase IV (CD26) Reveals its Functional Regulation and Enzymatic Mechanism Proc.Natl.Acad.Sci.USA, 100:5063-5068, 2003 Cited by PubMed Abstract: The membrane-bound glycoprotein dipeptidyl peptidase IV (DP IV, CD26) is a unique multifunctional protein, acting as receptor, binding and proteolytic molecule. We have determined the sequence and 1.8 A crystal structure of native DP IV prepared from porcine kidney. The crystal structure reveals a 2-2-2 symmetric tetrameric assembly which depends on the natively glycosylated beta-propeller blade IV. The crystal structure indicates that tetramerization of DP IV is a key mechanism to regulate its interaction with other components. Each subunit comprises two structural domains, the N-terminal eight-bladed beta-propeller with open Velcro topology and the C-terminal alpha/beta-hydrolase domain. Analogy with the structurally related POP and tricorn protease suggests that substrates access the buried active site through the beta-propeller tunnel while products leave the active site through a separate side exit. A dipeptide mimicking inhibitor complexed to the active site discloses key determinants for substrate recognition, including a Glu-Glu motif that distinguishes DP IV as an aminopeptidase and an oxyanion trap that binds and activates the P(2)-carbonyl oxygen necessary for efficient postproline cleavage. We discuss active and nonactive site-directed inhibition strategies of this pharmaceutical target protein. PubMed: 12690074DOI: 10.1073/pnas.0230620100 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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