6emi

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Crystal structure of a variant of human butyrylcholinesterase expressed in bacteria.

Structural highlights

6emi is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.476Å
Ligands:CL, EDO, PEG, PG4, PGE
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

Human butyrylcholinesterase is a performant stoichiometric bioscavenger of organophosphorous nerve agents. It is either isolated from outdated plasma or functionally expressed in eukaryotic systems. Here, we report the production of active human butyrylcholinesterase in a prokaryotic system after optimization of the primary sequence through the Protein Repair One Stop Shop process, a structure- and sequence-based algorithm for soluble bacterial expression of difficult eukaryotic proteins. The mutant enzyme was purified to homogeneity. Its kinetic parameters with substrate are similar to the endogenous human butyrylcholinesterase or recombinants produced in eukaryotic systems. The isolated protein was prone to crystallize and its 2.5-A X-ray structure revealed an active site gorge region identical to that of previously solved structures. The advantages of this alternate expression system, particularly for the generation of butyrylcholinesterase variants with nerve agent hydrolysis activity, are discussed.

Bacterial Expression of Human Butyrylcholinesterase as a Tool for Nerve Agent Bioscavengers Development.,Brazzolotto X, Igert A, Guillon V, Santoni G, Nachon F Molecules. 2017 Oct 27;22(11). pii: E1828. doi: 10.3390/molecules22111828. PMID:29077024[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
3 reviews cite this structure
Practically useful protein-design methods combining phylogenetic and atomistic calculations.
Weinstein et al. (2020)
2 more
7 other articles
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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Brazzolotto X, Igert A, Guillon V, Santoni G, Nachon F. Bacterial Expression of Human Butyrylcholinesterase as a Tool for Nerve Agent Bioscavengers Development. Molecules. 2017 Oct 27;22(11). pii: E1828. doi: 10.3390/molecules22111828. PMID:29077024 doi:http://dx.doi.org/10.3390/molecules22111828

Contents


PDB ID 6emi

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