3SX4

Crystal structure of human dpp-iv in complex with sa-(+)-3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(2-methoxyphenyl)- 2-methyl-5h-pyrrolo[3,4-b]pyridin-7(6h)-one


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.

Wang, W.Devasthale, P.Wang, A.Harrity, T.Egan, D.Morgan, N.Cap, M.Fura, A.Klei, H.E.Kish, K.Weigelt, C.Sun, L.Levesque, P.Li, Y.X.Zahler, R.Kirby, M.S.Hamann, L.G.

(2011) Bioorg Med Chem Lett 21: 6646-6651

  • DOI: https://doi.org/10.1016/j.bmcl.2011.09.074
  • Primary Citation of Related Structures:  
    3SWW, 3SX4

  • PubMed Abstract: 

    Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 μmol/kg in ob/ob mice.


  • Organizational Affiliation

    Metabolic Diseases Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl peptidase 4
A, B
753Homo sapiensMutation(s): 0 
Gene Names: DPP4ADCP2CD26
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-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, D
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KXA
Query on KXA

Download Ideal Coordinates CCD File 
J [auth A],
Q [auth B]
3-(aminomethyl)-4-(2,4-dichlorophenyl)-6-(2-methoxyphenyl)-2-methyl-5,6-dihydro-7H-pyrrolo[3,4-b]pyridin-7-one
C22 H19 Cl2 N3 O2
YFKUZVBMNGNFRI-UHFFFAOYSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
K [auth B],
L [auth B],
M [auth B],
N [auth B],
O [auth B],
P [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
KXA BindingDB:  3SX4 Ki: min: 3, max: 36 (nM) from 2 assay(s)
PDBBind:  3SX4 Ki: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.905α = 90
b = 67.854β = 90
c = 422.095γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
CBASSdata collection
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-10-26 
  • Deposition Author(s): Klei, H.E.

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-26
    Type: Initial release
  • Version 1.1: 2012-05-23
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 2.1: 2023-09-13
    Changes: Data collection, Database references, Refinement description, Structure summary