7CJG
Structural and kinetic characterization of Porphyromonas gingivalis glutaminyl cyclase
Summary for 7CJG
| Entry DOI | 10.2210/pdb7cjg/pdb |
| Related | 7CJE |
| Descriptor | Glutamine cyclotransferase-related protein, 5,6-DIMETHYLBENZIMIDAZOLE, GLYCEROL, ... (7 entities in total) |
| Functional Keywords | glutaminyl cyclase, pyroglutamate, prophyromonas gingivalis, antibiotic |
| Biological source | Porphyromonas gingivalis (strain ATCC BAA-308 / W83) |
| Total number of polymer chains | 2 |
| Total formula weight | 73972.77 |
| Authors | Ruiz-Carrillo, D.,Lamers, S.,Feng, Q.,Yu, S.,Sun, B.,Jiang, J.,Lukman, M. (deposition date: 2020-07-10, release date: 2021-05-05, Last modification date: 2023-11-29) |
| Primary citation | 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 Cited by 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: 33823093DOI: 10.1515/hsz-2020-0298 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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