4OC0

X-ray structure of of human glutamate carboxypeptidase II (GCPII) in a complex with CCIBzL, a urea-based inhibitor N~2~-[(1-carboxycyclopropyl)carbamoyl]-N~6~-(4-iodobenzoyl)-L-lysine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.161 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Structural characterization of P1'-diversified urea-based inhibitors of glutamate carboxypeptidase II.

Pavlicek, J.Ptacek, J.Cerny, J.Byun, Y.Skultetyova, L.Pomper, M.G.Lubkowski, J.Barinka, C.

(2014) Bioorg Med Chem Lett 24: 2340-2345

  • DOI: https://doi.org/10.1016/j.bmcl.2014.03.066
  • Primary Citation of Related Structures:  
    4OC0, 4OC1, 4OC2, 4OC3, 4OC4, 4OC5

  • PubMed Abstract: 

    Urea-based inhibitors of human glutamate carboxypeptidase II (GCPII) have advanced into clinical trials for imaging metastatic prostate cancer. In parallel efforts, agents with increased lipophilicity have been designed and evaluated for targeting GCPII residing within the neuraxis. Here we report the structural and computational characterization of six complexes between GCPII and P1'-diversified urea-based inhibitors that have the C-terminal glutamate replaced by more hydrophobic moieties. The X-ray structures are complemented by quantum mechanics calculations that provide a quantitative insight into the GCPII/inhibitor interactions. These data can be used for the rational design of novel glutamate-free GCPII inhibitors with tailored physicochemical properties.


  • Organizational Affiliation

    Institute of Biotechnology, Academy of Sciences of the Czech Republic, v.v.i., Laboratory of Structural Biology, Vídeňská 1083, 14220 Prague 4, Czech Republic.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutamate carboxypeptidase 2709Homo sapiensMutation(s): 0 
Gene Names: FOLHFOLH1GIG27NAALAD1PSMPSMA
EC: 3.4.17.21
UniProt & NIH Common Fund Data Resources
Find proteins for Q04609 (Homo sapiens)
Explore Q04609 
Go to UniProtKB:  Q04609
PHAROS:  Q04609
GTEx:  ENSG00000086205 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ04609
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
B, C, D
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2R7
Query on 2R7

Download Ideal Coordinates CCD File 
M [auth A]N~2~-[(1-carboxycyclopropyl)carbamoyl]-N~6~-(4-iodobenzoyl)-L-lysine
C18 H22 I N3 O6
VRNHYZLBDDWTFH-ZDUSSCGKSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
H [auth A]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
K [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
L [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
2R7 Binding MOAD:  4OC0 Ki: 318 (nM) from 1 assay(s)
BindingDB:  4OC0 Ki: 318 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.161 
  • R-Value Observed: 0.161 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.376α = 90
b = 129.938β = 90
c = 158.575γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-05-21
    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