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

Summary for 4OC0

• Entry DOI: 10.2210/pdb4oc0/pdb
• Related: 4OC1 4OC2 4OC3 4OC4 4OC5
• Descriptor: Glutamate carboxypeptidase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 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, ... (9 entities in total)
• Functional Keywords: hydrolase, metallopeptidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 83254.18

Authors

Pavlicek, J.,Ptacek, J.,Cerny, J.,Byun, Y.,Skultetyova, L.,Pomper, M.,Lubkowski, J.,Barinka, C. (deposition date: 2014-01-08, release date: 2014-05-21, Last modification date: 2024-10-16)

Primary citation

Pavlicek, J.,Ptacek, J.,Cerny, J.,Byun, Y.,Skultetyova, L.,Pomper, M.G.,Lubkowski, J.,Barinka, C.
Structural characterization of P1'-diversified urea-based inhibitors of glutamate carboxypeptidase II.
Bioorg.Med.Chem.Lett., 24:2340-2345, 2014

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.

PubMed: 24731280
DOI: 10.1016/j.bmcl.2014.03.066

Experimental method

X-RAY DIFFRACTION (1.85 Å)