2IIV

Human dipeptidyl peptidase 4 in complex with a diazepan-2-one inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 

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Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history. 


Literature

(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

Biftu, T., Feng, D., Qian, X., Liang, G.B., Kieczykowski, G., Eiermann, G., He, H., Leiting, B., Lyons, K., Petrov, A., Sinha-Roy, R., Zhang, B., Scapin, G., Patel, S., Gao, Y.D., Singh, S., Wu, J., Zhang, X., Thornberry, N.A., Weber, A.E.

(2007) Bioorg Med Chem Lett 17: 49-52

  • DOI: https://doi.org/10.1016/j.bmcl.2006.09.099
  • Primary Citation of Related Structures:  
    2IIT, 2IIV

  • PubMed Abstract: 

    Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.

    • Organizational Affiliation: 

    Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. Tesfaye_Biftu@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: DPP4, ADCP2, CD26
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
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
Binding Affinity Annotations 
IDSourceBinding Affinity
565 PDBBind:  2IIV IC50: 6.6 (nM) from 1 assay(s)
BindingDB:  2IIV IC50: 6.6 (nM) from 1 assay(s)
Binding MOAD:  2IIV IC50: 6.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.192α = 90
b = 125.777β = 90
c = 136.902γ = 90
Software Package:
Software NamePurpose
CNSrefinement
PDB_EXTRACTdata extraction
MAR345data collection
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing
CNXrefinement

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: 2006-11-28
    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