1ORV

Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 

wwPDB Validation 3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The Crystal Structure of Dipeptidyl Peptidase IV (CD26) Reveals its Functional Regulation and Enzymatic Mechanism

Engel, M.Hoffmann, T.Wagner, L.Wermann, M.Heiser, U.Kiefersauer, R.Huber, R.Bode, W.Demuth, H.U.Brandstetter, H.

(2003) Proc Natl Acad Sci U S A 100: 5063-5068

  • DOI: 10.1073/pnas.0230620100
  • Structures With Same Primary Citation

  • 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 ...

    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.


    Organizational Affiliation

    Max-Planck-Institut für Biochemie, Abt. Strukturforschung, D-82152 Martinsried, Germany.



Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
dipeptidyl peptidase IV
A, B, C, D
728Sus scrofaMutation(s): 0 
Gene Names: DPP4CD26
EC: 3.4.14.5
Find proteins for P22411 (Sus scrofa)
Go to UniProtKB:  P22411
Small Molecules
Ligands 3 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download CCD File 
A, B, C, D
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
BMA
Query on BMA

Download CCD File 
B, D
BETA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
 Ligand Interaction
SO4
Query on SO4

Download CCD File 
A, B, C, D
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62α = 112.76
b = 118.18β = 94.93
c = 133.59γ = 91.14
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
MAINphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History 

  • Version 1.0: 2003-05-06
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance