Structural highlights
6qae is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Gene: | BCHE, CHE1 (HUMAN) |
| Activity: | Cholinesterase, with EC number 3.1.1.8 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[CHLE_HUMAN] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:177400]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
Function
[CHLE_HUMAN] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.[1] [2]
Publication Abstract from PubMed
We have identified tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors. They are defined according to their chemical modularity, novel binding mode revealed by five solved crystal structures with human BChE, low cytotoxicity, and predicted permeability of the blood-brain barrier. Altogether, these factors indicate their potential as unique lead compounds for symptomatic therapy against Alzheimer's disease.
Tryptophan-derived butyrylcholinesterase inhibitors as promising leads against Alzheimer's disease.,Meden A, Knez D, Jukic M, Brazzolotto X, Grsic M, Pislar A, Zahirovic A, Kos J, Nachon F, Svete J, Gobec S, Groselj U Chem Commun (Camb). 2019 Mar 26;55(26):3765-3768. doi: 10.1039/c9cc01330j. PMID:30864579[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chilukuri N, Duysen EG, Parikh K, diTargiani R, Doctor BP, Lockridge O, Saxena A. Adenovirus-transduced human butyrylcholinesterase in mouse blood functions as a bioscavenger of chemical warfare nerve agents. Mol Pharmacol. 2009 Sep;76(3):612-7. doi: 10.1124/mol.109.055665. Epub 2009 Jun, 19. PMID:19542320 doi:10.1124/mol.109.055665
- ↑ Amitay M, Shurki A. The structure of G117H mutant of butyrylcholinesterase: nerve agents scavenger. Proteins. 2009 Nov 1;77(2):370-7. doi: 10.1002/prot.22442. PMID:19452557 doi:10.1002/prot.22442
- ↑ Meden A, Knez D, Jukic M, Brazzolotto X, Grsic M, Pislar A, Zahirovic A, Kos J, Nachon F, Svete J, Gobec S, Groselj U. Tryptophan-derived butyrylcholinesterase inhibitors as promising leads against Alzheimer's disease. Chem Commun (Camb). 2019 Mar 26;55(26):3765-3768. doi: 10.1039/c9cc01330j. PMID:30864579 doi:http://dx.doi.org/10.1039/c9cc01330j
