3FVY

Crystal structure of human Dipeptidyl Peptidase III


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.172 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Entropy-driven binding of opioid peptides induces a large domain motion in human dipeptidyl peptidase III.

Bezerra, G.A.Dobrovetsky, E.Viertlmayr, R.Dong, A.Binter, A.Abramic, M.Macheroux, P.Dhe-Paganon, S.Gruber, K.

(2012) Proc Natl Acad Sci U S A 109: 6525-6530

  • DOI: https://doi.org/10.1073/pnas.1118005109
  • Primary Citation of Related Structures:  
    3FVY, 3T6B, 3T6J

  • PubMed Abstract: 

    Opioid peptides are involved in various essential physiological processes, most notably nociception. Dipeptidyl peptidase III (DPP III) is one of the most important enkephalin-degrading enzymes associated with the mammalian pain modulatory system. Here we describe the X-ray structures of human DPP III and its complex with the opioid peptide tynorphin, which rationalize the enzyme's substrate specificity and reveal an exceptionally large domain motion upon ligand binding. Microcalorimetric analyses point at an entropy-dominated process, with the release of water molecules from the binding cleft ("entropy reservoir") as the major thermodynamic driving force. Our results provide the basis for the design of specific inhibitors that enable the elucidation of the exact role of DPP III and the exploration of its potential as a target of pain intervention strategies.


  • Organizational Affiliation

    Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl-peptidase 3728Homo sapiensMutation(s): 1 
Gene Names: DPP3
EC: 3.4.14.4
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NY33 (Homo sapiens)
Explore Q9NY33 
Go to UniProtKB:  Q9NY33
PHAROS:  Q9NY33
GTEx:  ENSG00000254986 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NY33
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.172 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.812α = 90
b = 151.378β = 100.04
c = 53.721γ = 90
Software Package:
Software NamePurpose
HKL-3000data collection
PHASESphasing
REFMACrefinement
Cootmodel building
HKL-3000data reduction
HKL-3000data scaling

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-03
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2015-02-25
    Changes: Database references
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description