2JBJ

membrane-bound glutamate carboxypeptidase II (GCPII) in complex with 2-PMPA (2-phosphonoMethyl-pentanedioic acid)

2JBJ の概要

• エントリーDOI: 10.2210/pdb2jbj/pdb
• 関連するPDBエントリー: 1Z8L 2C6C 2C6G 2C6P 2CIJ 2JBK
• 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: multifunctional enzyme, neurodegenerative disease, glycoprotein, metal-binding, signal-anchor, hydrolase, naaladase, dipeptidase, polymorphism, zinc, psma, antigen, membrane, protease, peptidase, transmembrane, metal- binding, metalloprotease, prostate cancer, carboxypeptidase, alternative splicing
• 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: 82732.73

構造登録者

Mesters, J.R.,Henning, K.,Hilgenfeld, R. (登録日: 2006-12-07, 公開日: 2006-12-18, 最終更新日: 2024-10-16)

主引用文献

Mesters, J.R.,Henning, K.,Hilgenfeld, R.
Human Glutamate Carboxypeptidase II Inhibition: Structures of Gcpii in Complex with Two Potent Inhibitors, Quisqualate and 2-Pmpa.
Acta Crystallogr.,Sect.D, 63:508-, 2007

PubMed Abstract: Human glutamate carboxypeptidase II (GCPII) occurs in the central nervous system as well as in human prostate (where it is called prostate-specific membrane antigen; PSMA). Inhibitors of the enzyme have been shown to provide neuroprotection, but may also be useful for the detection, imaging and treatment of prostate cancer. Crystal structures were determined of the extracellular part of GCPII (amino-acid residues 44-750) in complex with two potent inhibitors, quisqualate and 2-PMPA (the strongest GCPII inhibitor to date), at resolutions of 3.0 and 2.2 A, respectively. In addition, models were constructed for binding of the inhibitors willardiine, homoibotenate, L-2-amino-4-phosphonobutanoic acid and L-serine-O-sulfate to the S1' site of the enzyme. The common denominator for high-affinity binding to the S1' site is the formation of two strong salt bridges.

PubMed: 17372356
DOI: 10.1107/S090744490700902X

実験手法

X-RAY DIFFRACTION (2.19 Å)