9I4W
Structure of carbamoylated recombinant human butyrylcholinesterase by the biscarbamte 5-(1-hydroxy-2-(piperidin-1-yl)ethyl)-1,3-phenylene bis(piperidine-1-carboxylate)
This is a non-PDB format compatible entry.
Summary for 9I4W
| Entry DOI | 10.2210/pdb9i4w/pdb |
| Descriptor | Cholinesterase, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total) |
| Functional Keywords | butyrylcholinesterase, inhibitor, complex, carbamate, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 63903.56 |
| Authors | Brazzolotto, X.,Bosak, A.,Nachon, F. (deposition date: 2025-01-27, release date: 2026-02-04, Last modification date: 2026-06-03) |
| Primary citation | Matosevic, A.,Marakovic, N.,Baric, D.,Igert, A.,Brazzolotto, X.,Kovarik, Z.,Bosak, A. Integrative structural and kinetic analysis of the molecular basis for reduced carbamate inhibition in atypical butyrylcholinesterase. Chem.Biol.Interact., 435:112134-112134, 2026 Cited by PubMed Abstract: Butyrylcholinesterase (BChE) plays a key role in cholinergic transmission and the metabolism of various drugs, making its regulation a promising therapeutic strategy for several diseases, including Alzheimer's disease. Selective inhibition of BChE helps regulate brain acetylcholine levels. However, genetic polymorphisms in the BCHE gene, particularly the Asp70Gly mutation in atypical BChE, can impact treatment outcomes. This study compares the inhibitory potency of 13 carbamates against atypical and usual BChE. Using molecular docking, quantum chemical cluster calculations, and crystallization of wild-type BChE with the most potent carbamate, we identified key differences in carbamylation mechanisms. Atypical BChE shows a less favorable enzyme-inhibitor complex orientation, lacking the hydrogen bond stabilization of the reactive carbonyl oxygen. Additionally, Asp70 in usual BChE contributes to stabilizing the non-reactive carbamate group, whereas Gly70 in atypical BChE is too distant to form such interactions. PubMed: 42097478DOI: 10.1016/j.cbi.2026.112134 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.44 Å) |
Structure validation
Download full validation report
