7cje

Structural and kinetic characterization of Porphyromonas gingivalis glutaminyl cyclase

spinqualitylabelsall models 7cje, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7cje is a 2 chain structure with sequence from Porphyromonas gingivalis W83. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.950007Å Ligands: GOL, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q7MT37_PORGI Publication Abstract from PubMed 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 A 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(149), Glu(182), Asp(183), Asp(218), Asp(267) and His(299). In addition, we could observe that a non-conserved Trp(193) 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. Structural and kinetic characterization of Porphyromonas gingivalis glutaminyl cyclase.,Lamers S, Feng Q, Cheng Y, Yu S, Sun B, Lukman M, Jiang J, Ruiz-Carrillo D Biol Chem. 2021 Apr 7. pii: hsz-2020-0298. doi: 10.1515/hsz-2020-0298. PMID:33823093 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutaminyl cyclase

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