2HHA

The structure of DPP4 in complex with an oxadiazole inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history


Literature

Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors.

Xu, J.Wei, L.Mathvink, R.J.Edmondson, S.D.Eiermann, G.J.He, H.Leone, J.F.Leiting, B.Lyons, K.A.Marsilio, F.Patel, R.A.Patel, S.B.Petrov, A.Scapin, G.Wu, J.K.Thornberry, N.A.Weber, A.E.

(2006) Bioorg Med Chem Lett 16: 5373-5377

  • DOI: https://doi.org/10.1016/j.bmcl.2006.07.061
  • Primary Citation of Related Structures:  
    2HHA

  • PubMed Abstract: 

    A novel series of oxadiazole based amides have been shown to be potent DPP-4 inhibitors. The optimized compound 43 exhibited excellent selectivity over a variety of DPP-4 homologs.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. Jinyou_Xu@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hypothetical protein DPP4
A, B
728Homo sapiensMutation(s): 1 
Gene Names: DPP4
EC: 3.4.14.5
UniProt & NIH Common Fund Data Resources
Find proteins for P27487 (Homo sapiens)
Explore P27487 
Go to UniProtKB:  P27487
PHAROS:  P27487
GTEx:  ENSG00000197635 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27487
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, F
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G07375KG
GlyCosmos:  G07375KG
GlyGen:  G07375KG
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D, E, G, H, I
D, E, G, H, I, J, K
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3TP
Query on 3TP

Download Ideal Coordinates CCD File 
P [auth A],
T [auth B]
(2S,3S)-3-{3-[4-(METHYLSULFONYL)PHENYL]-1,2,4-OXADIAZOL-5-YL}-1-OXO-1-PYRROLIDIN-1-YLBUTAN-2-AMINE
C17 H22 N4 O4 S
SQCDMTZMCHZYGO-FZMZJTMJSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
L [auth A]
M [auth A]
N [auth A]
Q [auth B]
R [auth B]
L [auth A],
M [auth A],
N [auth A],
Q [auth B],
R [auth B],
S [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
O [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3TP PDBBind:  2HHA IC50: 122 (nM) from 1 assay(s)
BindingDB:  2HHA IC50: 122 (nM) from 1 assay(s)
Binding MOAD:  2HHA IC50: 122 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.971α = 90
b = 125.584β = 90
c = 136.716γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2006-09-19 
  • Deposition Author(s): Scapin, G.

Revision History  (Full details and data files)

  • Version 1.0: 2006-09-19
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2021-10-20
    Changes: Database references, Structure summary
  • Version 2.2: 2023-08-30
    Changes: Data collection, Refinement description