7CJG

Structural and kinetic characterization of Porphyromonas gingivalis glutaminyl cyclase

7CJG の概要

• エントリーDOI: 10.2210/pdb7cjg/pdb
• 関連するPDBエントリー: 7CJE
• 分子名称: Glutamine cyclotransferase-related protein, 5,6-DIMETHYLBENZIMIDAZOLE, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: glutaminyl cyclase, pyroglutamate, prophyromonas gingivalis, antibiotic
• 由来する生物種: Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73972.77

構造登録者

Ruiz-Carrillo, D.,Lamers, S.,Feng, Q.,Yu, S.,Sun, B.,Jiang, J.,Lukman, M. (登録日: 2020-07-10, 公開日: 2021-05-05, 最終更新日: 2023-11-29)

主引用文献

Lamers, S.,Feng, Q.,Cheng, Y.,Yu, S.,Sun, B.,Lukman, M.,Jiang, J.,Ruiz-Carrillo, D.
Structural and kinetic characterization of Porphyromonas gingivalis glutaminyl cyclase.
Biol.Chem., 402:759-768, 2021

PubMed Abstract: is a bacterial species known to be involved in the pathogenesis of chronic periodontitis, that more recently has been as well associated with Alzheimer's disease. expresses a glutaminyl cyclase (PgQC) whose human ortholog is known to participate in the beta amyloid peptide metabolism. We have elucidated the crystal structure of PgQC at 1.95 Å resolution in unbound and in inhibitor-complexed forms. The structural characterization of PgQC confirmed that PgQC displays a mammalian fold rather than a bacterial fold. Our biochemical characterization indicates that PgQC uses a mammalian-like catalytic mechanism enabled by the residues Asp, Glu, Asp, Asp, Asp and His. In addition, we could observe that a non-conserved Trp may drive differences in the binding affinity of ligands which might be useful for drug development. With a screening of a small molecule library, we have identified a benzimidazole derivative rendering PgQC inhibition in the low micromolar range that might be amenable for further medicinal chemistry development.

PubMed: 33823093
DOI: 10.1515/hsz-2020-0298

実験手法

X-RAY DIFFRACTION (2 Å)