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

4OC0 の概要

• エントリーDOI: 10.2210/pdb4oc0/pdb
• 関連するPDBエントリー: 4OC1 4OC2 4OC3 4OC4 4OC5
• 分子名称: 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)
• 機能のキーワード: hydrolase, metallopeptidase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type II membrane protein. Isoform PSMA': Cytoplasm: Q04609
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 83254.18

構造登録者

Pavlicek, J.,Ptacek, J.,Cerny, J.,Byun, Y.,Skultetyova, L.,Pomper, M.,Lubkowski, J.,Barinka, C. (登録日: 2014-01-08, 公開日: 2014-05-21, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)