9QPU
Structure of human butyrylcholinesterase inhibited by the Ellman's reaction product, 2-[(3-carboxy-4-nitrophenyl)disulfanyl]ethyl-trimethylazanium
This is a non-PDB format compatible entry.
Summary for 9QPU
| Entry DOI | 10.2210/pdb9qpu/pdb |
| Descriptor | Cholinesterase, SODIUM ION, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total) |
| Functional Keywords | butyrylcholinesterase, complex, inhibitor, ellman, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 64453.30 |
| Authors | Brazzolotto, X.,Stojan, J. (deposition date: 2025-03-29, release date: 2025-11-19, Last modification date: 2025-11-26) |
| Primary citation | Stojan, J.,Brazzolotto, X. The product of Ellman's reaction inhibits cholinesterases. Protein Sci., 34:e70371-e70371, 2025 Cited by PubMed Abstract: Kinetic and crystallographic studies reveal that the binding of the thiocholine-thionitrobenzoic acid product, released during the measurement of thioester-analog substrates hydrolysis according to Ellman's method, inhibits cholinesterases by a pure competitive mechanism. This can only be recorded as the progressive accumulation of the product upon subsequent additions of substrate aliquots. A wide affinity variation was observed among several tested enzymes, with the highest values found in human butyrylcholinesterase and Torpedo acetylcholinesterase. Nearly two orders of magnitude lower affinities were determined with human, mouse, and electrophorus acetylcholinesterases, and human atypical butyrylcholinesterase. These findings can be explained by the unexpected accommodation of the thiocholine-thionitrobenzoic acid in the active site of human butyrylcholinesterase, with the positively charged trimethylammonium choline pointing to the enzyme's peripheral site. At the same time, the carboxyl group of the nitrobenzoic moiety interacts with the enzyme's oxyanion hole. This explains the virtual absence of product inhibition in atypical human butyrylcholinesterase (D70G), purified or in plasma. PubMed: 41229096DOI: 10.1002/pro.70371 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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