3C43

Human dipeptidyl peptidase IV/CD26 in complex with a flouroolefin inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 3.1 of the entry. See complete history


Literature

Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors

Edmondson, S.D.Wei, L.Xu, J.Shang, J.Xu, S.Pang, J.Chaudhary, A.Dean, D.C.He, H.Leiting, B.Lyons, K.A.Patel, R.A.Patel, S.B.Scapin, G.Wu, J.K.Beconi, M.G.Thornberry, N.A.Weber, A.E.

(2008) Bioorg Med Chem Lett 18: 2409-2413

  • DOI: https://doi.org/10.1016/j.bmcl.2008.02.050
  • Primary Citation of Related Structures:  
    3C43, 3C45

  • PubMed Abstract: 

    The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liability for this class of DPP-4 inhibitors.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl peptidase 4 soluble form
A, B
728Homo sapiensMutation(s): 1 
Gene Names: DPP4ADCP2CD26
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
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, D, E, F, G
C, D, E, F, G, H, I, J, K
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
315
Query on 315

Download Ideal Coordinates CCD File 
O [auth A],
S [auth B]
(2S,3S)-4-cyclopropyl-3-{(3R,5R)-3-[2-fluoro-4-(methylsulfonyl)phenyl]-1,2,4-oxadiazolidin-5-yl}-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxobutan-2-amine
C20 H28 F2 N4 O4 S
PTAHVQJZNFGPHN-WFWWEWPISA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
L [auth A]
M [auth A]
N [auth A]
P [auth B]
Q [auth B]
L [auth A],
M [auth A],
N [auth A],
P [auth B],
Q [auth B],
R [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
315 PDBBind:  3C43 IC50: 19 (nM) from 1 assay(s)
BindingDB:  3C43 IC50: 19 (nM) from 1 assay(s)
Binding MOAD:  3C43 IC50: 19 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.864α = 90
b = 125.835β = 90
c = 136.712γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
CNXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 3.0: 2021-10-20
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Source and taxonomy, Structure summary
  • Version 3.1: 2023-08-30
    Changes: Data collection, Refinement description