4X3R

Avi-GCPII structure in complex with FITC-conjugated GCPII-specific inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.180 
  • R-Value Work: 0.148 
  • R-Value Observed: 0.149 

wwPDB Validation 3D Report Full Report



Literature

Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II.

Tykvart, J.Schimer, J.Jancarik, A.Barinkova, J.Navratil, V.Starkova, J.Sramkova, K.Konvalinka, J.Majer, P.Sacha, P.

(2015) J Med Chem 58: 4357-4363

  • DOI: 10.1021/acs.jmedchem.5b00278
  • Structures With Same Primary Citation

  • PubMed Abstract: 
  • We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more activ ...

    We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.


    Organizational Affiliation

    ‡Department of Biochemistry, Faculty of Science, Charles University, Albertov 6, Prague 2, 128 43, Czech Republic.



Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Glutamate carboxypeptidase 2
A
739Homo sapiensMutation(s): 0 
Gene Names: FOLH1FOLHNAALAD1PSMPSMAGIG27
EC: 3.4.17.21
Find proteins for Q04609 (Homo sapiens)
Go to UniProtKB:  Q04609
NIH Common Fund Data Resources
PHAROS  Q04609
Protein Feature View
  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
686
Query on 686

Download CCD File 
A
N-({(1S)-5-[(4-bromobenzyl)({6-[4-(4-{4-[4-carboxy-3-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoyl]piperazin-1-yl}phenyl)piperazin-1-yl]pyridin-3-yl}carbonyl)amino]-1-carboxypentyl}carbamoyl)-L-glutamic acid
C60 H59 Br N8 O14
HNPUHOJFAXMPAU-GTMCEHENSA-N
 Ligand Interaction
NAG
Query on NAG

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A
N-ACETYL-D-GLUCOSAMINE
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
 Ligand Interaction
BMA
Query on BMA

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A
BETA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-RWOPYEJCSA-N
 Ligand Interaction
MAN
Query on MAN

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A
ALPHA-D-MANNOSE
C6 H12 O6
WQZGKKKJIJFFOK-PQMKYFCFSA-N
 Ligand Interaction
ZN
Query on ZN

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A
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
 Ligand Interaction
CA
Query on CA

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A
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
 Ligand Interaction
CL
Query on CL

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A
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
 Ligand Interaction
External Ligand Annotations 
IDBinding Affinity (Sequence Identity %)
686Ki:  0.009999999776482582   nM  BindingDB
686Ki:  0.00860000029206276   nM  Binding MOAD
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Free: 0.180 
  • R-Value Work: 0.148 
  • R-Value Observed: 0.149 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.71α = 90
b = 130.163β = 90
c = 159.536γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History 

  • Version 1.0: 2015-10-14
    Type: Initial release