4YU9

Crystal Structure of double mutant Y115E Y117E human Glutaminyl Cyclase

4YU9 の概要

• エントリーDOI: 10.2210/pdb4yu9/pdb
• 分子名称: Glutaminyl-peptide cyclotransferase, ZINC ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: alzheimer disease, drug target, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted : Q16769
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 113883.27

構造登録者

Di Pisa, F.,Pozzi, C.,Benvenuti, M.,Mangani, S. (登録日: 2015-03-18, 公開日: 2015-08-05, 最終更新日: 2024-05-08)

主引用文献

DiPisa, F.,Pozzi, C.,Benvenuti, M.,Andreini, M.,Marconi, G.,Mangani, S.
The soluble Y115E-Y117E variant of human glutaminyl cyclase is a valid target for X-ray and NMR screening of inhibitors against Alzheimer disease.
Acta Crystallogr.,Sect.F, 71:986-992, 2015

PubMed Abstract: Recent developments in molecular pathology and genetics have allowed the identification of human glutaminyl cyclase (hQC) among the abnormal proteins involved in many neurodegenerative disorders. Difficulties in obtaining large quantities of pure protein may limit the use of crystallographic screening for drug development on this target. Site-directed mutagenesis experiments have led to the identification of some solvent-exposed residues that are absolutely critical to achieve increased solubility and to avoid precipitation of the enzyme in inclusion bodies when expressed in Escherichia coli. The designed variant Y115E-Y117E has been found to be able to provide large amounts of monodisperse, pure hQC from an E. coli expression system. To validate the use of the artificial construct as a target for large-scale X-ray and NMR screening campaigns in the search for new inhibitors of hQC, the X-ray crystal structures of the hQC Y115E-Y117E variant and of its adduct with the inhibitor PBD-150 were determined.

PubMed: 26249687
DOI: 10.1107/S2053230X15010389

実験手法

X-RAY DIFFRACTION (2.1 Å)