3KWJ

Structure of human DPP-IV with (2S,3S,11bS)-3-(3-Fluoromethyl-phenyl)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ylamine

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Aryl- and heteroaryl-substituted aminobenzo[a]quinolizines as dipeptidyl peptidase IV inhibitors.

Boehringer, M., Fischer, H., Hennig, M., Hunziker, D., Huwyler, J., Kuhn, B., Loeffler, B.M., Luebbers, T., Mattei, P., Narquizian, R., Sebokova, E., Sprecher, U., Wessel, H.P.

(2010) Bioorg Med Chem Lett 20: 1106-1108

  • DOI: https://doi.org/10.1016/j.bmcl.2009.12.025
  • Primary Citation of Related Structures:  
    3KWJ

  • PubMed Abstract: 

    Synthesis and SAR are described for a structurally distinct class of DPP-IV inhibitors based on aminobenzo[a]quinolizines bearing (hetero-)aromatic substituents in the S1 specificity pocket. The m-(fluoromethyl)-phenyl derivative (S,S,S)-2g possesses the best fit in the S1 pocket. However, (S,S,S)-2i, bearing a more hydrophilic 5-methyl-pyridin-2-yl residue as substituent for the S1 pocket, displays excellent in vivo activity and superior drug-like properties.

    • Organizational Affiliation: 

    F Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl peptidase 4 soluble form
A, B
728Homo sapiensMutation(s): 0 
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
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
23Q BindingDB:  3KWJ IC50: 0.5 (nM) from 1 assay(s)
PDBBind:  3KWJ IC50: 0.5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.199α = 90
b = 68.957β = 90
c = 421.562γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-15
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.3: 2020-09-09
    Changes: Structure summary