2GMV

PEPCK complex with a GTP-competitive inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

C-8 Modifications of 3-alkyl-1,8-dibenzylxanthines as inhibitors of human cytosolic phosphoenolpyruvate carboxykinase.

Pietranico, S.L.Foley, L.H.Huby, N.Yun, W.Dunten, P.Vermeulen, J.Wang, P.Toth, K.Ramsey, G.Gubler, M.L.Wertheimer, S.J.

(2007) Bioorg Med Chem Lett 17: 3835-3839

  • DOI: https://doi.org/10.1016/j.bmcl.2007.05.013
  • Primary Citation of Related Structures:  
    2GMV

  • PubMed Abstract: 

    New modifications on the C-8 4-aminobenzyl unit of the previously reported 3-alkyl-1,8-dibenzylxanthine inhibitors of cPEPCK are presented. The most active compound reported here is the 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid amide derivative 2 with an IC(50) of 0.29+/-0.08 microM. An X-ray analysis of a heteroaromatic sulfonamide is presented showing a new pi-pi interaction.


  • Organizational Affiliation

    Department of Discovery Chemistry, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphoenolpyruvate carboxykinase, cytosolic
A, B
625Homo sapiensMutation(s): 4 
Gene Names: PCK1
EC: 4.1.1.32
UniProt & NIH Common Fund Data Resources
Find proteins for P35558 (Homo sapiens)
Explore P35558 
Go to UniProtKB:  P35558
PHAROS:  P35558
GTEx:  ENSG00000124253 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35558
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UN8
Query on UN8

Download Ideal Coordinates CCD File 
E [auth A]N-(4-{[3-BUTYL-1-(2-FLUOROBENZYL)-2,6-DIOXO-2,3,6,7-TETRAHYDRO-1H-PURIN-8-YL]METHYL}PHENYL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE
C27 H28 F N7 O4 S
OWJCXBGUTOMZTE-UHFFFAOYSA-N
PEP
Query on PEP

Download Ideal Coordinates CCD File 
D [auth A],
G [auth B]
PHOSPHOENOLPYRUVATE
C3 H5 O6 P
DTBNBXWJWCWCIK-UHFFFAOYSA-N
MN
Query on MN

Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]
MANGANESE (II) ION
Mn
WAEMQWOKJMHJLA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PEP BindingDB:  2GMV Ki: 2.89e+5 (nM) from 1 assay(s)
UN8 PDBBind:  2GMV IC50: 630 (nM) from 1 assay(s)
Binding MOAD:  2GMV IC50: 630 (nM) from 1 assay(s)
BindingDB:  2GMV IC50: 630 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.217 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.011α = 90
b = 66.134β = 145.09
c = 137.36γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data scaling
MOLREPphasing
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2007-05-29 
  • Deposition Author(s): Dunten, P.

Revision History  (Full details and data files)

  • Version 1.0: 2007-05-29
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-07-24
    Changes: Data collection, Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations