4X3R

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

Summary for 4X3R

• Entry DOI: 10.2210/pdb4x3r/pdb
• Descriptor: Glutamate carboxypeptidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: glycoprotein, metallopeptidase, inhibitor, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane ; Single-pass type II membrane protein . Isoform PSMA': Cytoplasm: Q04609
• Total number of polymer chains: 1
• Total formula weight: 87653.81

Authors

Tykvart, J.,Konvalinka, J. (deposition date: 2014-12-01, release date: 2015-10-14, Last modification date: 2024-01-10)

Primary citation

Tykvart, J.,Schimer, J.,Jancarik, A.,Barinkova, J.,Navratil, V.,Starkova, J.,Sramkova, K.,Konvalinka, J.,Majer, P.,Sacha, P.
Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II.
J.Med.Chem., 58:4357-4363, 2015

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 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.

PubMed: 25923815
DOI: 10.1021/acs.jmedchem.5b00278

Experimental method

X-RAY DIFFRACTION (1.86 Å)