Structural and kinetic characterization of Porphyromonas gingivalis glutaminyl cyclase

Sebastiaan Lamers, Qiaoli Feng, Yili Cheng, Sihong Yu, Bo Sun, Maxwell Lukman, Jie Jiang, David Ruiz-Carrillo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Porphyromonas gingivalis 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. P. gingivalis 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 Asp149, Glu182, Asp183, Asp218, Asp267 and His299. In addition, we could observe that a non-conserved Trp193 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.

Original languageEnglish
Pages (from-to)759-768
Number of pages10
JournalBiological Chemistry
Issue number7
Publication statusPublished - 1 Jun 2021


  • 5,6-dimethylbenzimid-azole
  • Alzheimer’s disease
  • Glutaminyl cyclase
  • Periodontitis
  • Porphyromonas gingivalis
  • Pyroglutamate
  • Rossmann fold


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