8CC7
Mouse serotonin 5-HT3A receptor in complex with PZ-1939
Summary for 8CC7
| Entry DOI | 10.2210/pdb8cc7/pdb |
| EMDB information | 16557 |
| Descriptor | 5-hydroxytryptamine receptor 3A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | ion channel, receptor, plgic, transport protein |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 5 |
| Total formula weight | 325898.24 |
| Authors | Lopez-Sanchez, U.,Nury, H. (deposition date: 2023-01-26, release date: 2023-10-11, Last modification date: 2024-10-16) |
| Primary citation | Grychowska, K.,Lopez-Sanchez, U.,Vitalis, M.,Canet, G.,Satala, G.,Olejarz-Maciej, A.,Golebiowska, J.,Kurczab, R.,Pietrus, W.,Kubacka, M.,Moreau, C.,Walczak, M.,Blicharz-Futera, K.,Bento, O.,Bantreil, X.,Subra, G.,Bojarski, A.J.,Lamaty, F.,Becamel, C.,Zussy, C.,Chaumont-Dubel, S.,Popik, P.,Nury, H.,Marin, P.,Givalois, L.,Zajdel, P. Superiority of the Triple-Acting 5-HT 6 R/5-HT 3 R Antagonist and MAO-B Reversible Inhibitor PZ-1922 over 5-HT 6 R Antagonist Intepirdine in Alleviation of Cognitive Deficits in Rats. J.Med.Chem., 66:14928-14947, 2023 Cited by PubMed Abstract: The multifactorial origin and neurochemistry of Alzheimer's disease (AD) call for the development of multitarget treatment strategies. We report a first-in-class triple acting compound that targets serotonin type 6 and 3 receptors (5-HT-Rs) and monoamine oxidase type B (MAO-B) as an approach for treating AD. The key structural features required for MAO-B inhibition and 5-HTR antagonism and interaction with 5-HTR were determined using molecular dynamic simulations and cryo-electron microscopy, respectively. Bioavailable reversed scopolamine-induced cognitive deficits in the novel object recognition test. Furthermore, it displayed superior pro-cognitive properties compared to intepirdine (a 5-HTR antagonist) in the AD model, which involved intracerebroventricular injection of an oligomeric solution of amyloid-β peptide (oAβ) in the T-maze test in rats. , but not intepirdine, restored levels of biomarkers characteristic of the debilitating effects of oAβ. These data support the potential of a multitarget approach involving the joint modulation of 5-HTR/5-HTR/MAO-B in AD. PubMed: 37797083DOI: 10.1021/acs.jmedchem.3c01482 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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