4G1F

Crystal Structure of human Dipeptidyl Peptidase IV in complex with a pyridopyrimidinedione analogue

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history. 


Literature

Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors.

Lam, B., Zhang, Z., Stafford, J.A., Skene, R.J., Shi, L., Gwaltney, S.L.

(2012) Bioorg Med Chem Lett 22: 6628-6631

  • DOI: https://doi.org/10.1016/j.bmcl.2012.08.110
  • Primary Citation of Related Structures:  
    4G1F

  • PubMed Abstract: 

    Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and selective DPP-4 inhibitors.

    • Organizational Affiliation: 

    Takeda California, 10410 Science Center Drive, San Diego, CA 92121, USA. blam@takedasd.com


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dipeptidyl peptidase 4
A, B, C, D
740Homo sapiensMutation(s): 0 
Gene Names: ADCP2, CD26, 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
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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
E, F, G, H, I
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
0WG
Query on 0WG
Download Ideal Coordinates CCD File 
J [auth A],
O [auth B],
T [auth C],
W [auth D]		7-amino-6-(aminomethyl)-5-(2-bromophenyl)-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione
C16 H16 Br N5 O2
JGBNONXELAWFNR-UHFFFAOYSA-N
NAG
Query on NAG
Download Ideal Coordinates CCD File 
K [auth A]
L [auth A]
M [auth A]
N [auth A]
P [auth B]
K [auth A],
L [auth A],
M [auth A],
N [auth A],
P [auth B],
Q [auth B],
R [auth B],
S [auth B],
U [auth C],
V [auth C],
X [auth D],
Y [auth D]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
0WG BindingDB:  4G1F IC50: 17 (nM) from 1 assay(s)
PDBBind:  4G1F IC50: 17 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.209 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 121.622α = 90
b = 121.362β = 114.63
c = 143.257γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-02-27
    Type: Initial release
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: 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