3D7H

A high resolution crystal structure of human glutamate carboxypeptidase II (GCPII) in a complex with DCIBzL, a urea-based inhibitor

3D7H の概要

• エントリーDOI: 10.2210/pdb3d7h/pdb
• 関連するPDBエントリー: 3D7D 3D7F 3D7G
• 分子名称: 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)
• 機能のキーワード: prostate specific membrane antigen (psma); metallopeptidase; folate hydrolase; glutamate carboxypeptidase ii; naaladase, dcibzl, urea-based inhibitor, carboxypeptidase, dipeptidase, glycoprotein, hydrolase, membrane, metal-binding, metalloprotease, multifunctional enzyme, protease, signal-anchor, transmembrane
• 由来する生物種: Homo sapiens
• 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: 83462.34

構造登録者

Lubkowski, J.,Barinka, C. (登録日: 2008-05-21, 公開日: 2008-12-30, 最終更新日: 2024-10-16)

主引用文献

Barinka, C.,Byun, Y.,Dusich, C.L.,Banerjee, S.R.,Chen, Y.,Castanares, M.,Kozikowski, A.P.,Mease, R.C.,Pomper, M.G.,Lubkowski, J.
Interactions between Human Glutamate Carboxypeptidase II and Urea-Based Inhibitors: Structural Characterization
J.Med.Chem., 51:7737-7743, 2008

PubMed Abstract: Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate an invariant glutarate moiety within the S1' pocket of the enzyme. The ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S1 pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that can be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity.

PubMed: 19053759
DOI: 10.1021/jm800765e

実験手法

X-RAY DIFFRACTION (1.55 Å)