Axelsen_1994_Prot.Sci_3_188

Reference

Title : Structure and dynamics of the active site gorge of acetylcholinesterase: synergistic use of molecular dynamics simulation and X-ray crystallography - Axelsen_1994_Prot.Sci_3_188
Author(s) : Axelsen PH , Harel M , Silman I , Sussman JL
Ref : Protein Science , 3 :188 , 1994
Abstract : The active site of acetylcholinesterase (AChE) from Torpedo californica is located 20 A from the enzyme surface at the bottom of a narrow gorge. To understand the role of this gorge in the function of AChE, we have studied simulations of its molecular dynamics. When simulations were conducted with pure water filling the gorge, residues in the vicinity of the active site deviated quickly and markedly from the crystal structure. Further study of the original crystallographic data suggests that a bis-quaternary decamethonium (DECA) ion, acquired during enzyme purification, residues in the gorge. There is additional electron density within the gorge that may represent small bound cations. When DECA and 2 cations are placed within the gorge, the simulation and the crystal structure are dramatically reconciled. The small cations, more so than DECA, appear to stabilize part of the gorge wall through electrostatic interactions. This part of the gorge wall is relatively thin and may regulate substrate, product, and water movement through the active site.
ESTHER : Axelsen_1994_Prot.Sci_3_188
PubMedSearch : Axelsen_1994_Prot.Sci_3_188
PubMedID: 8003956

Related information

Citations formats

Axelsen PH, Harel M, Silman I, Sussman JL (1994)
Structure and dynamics of the active site gorge of acetylcholinesterase: synergistic use of molecular dynamics simulation and X-ray crystallography
Protein Science 3 :188

Axelsen PH, Harel M, Silman I, Sussman JL (1994)
Protein Science 3 :188

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    [paper] => Axelsen_1994_Prot.Sci_3_188
    [author] => Axelsen PH || Harel M || Silman I || Sussman JL
    [year] => 1994
    [title] => Structure and dynamics of the active site gorge of acetylcholinesterase: synergistic use of molecular dynamics simulation and X-ray crystallography
    [journal] => Protein Science
    [volume] => 3
    [page] => 188
    [medline] => 8003956
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            [content] => The active site of acetylcholinesterase (AChE) from Torpedo californica is located 20 A from the enzyme surface at the bottom of a narrow gorge. To understand the role of this gorge in the function of AChE, we have studied simulations of its molecular dynamics. When simulations were conducted with pure water filling the gorge, residues in the vicinity of the active site deviated quickly and markedly from the crystal structure. Further study of the original crystallographic data suggests that a bis-quaternary decamethonium (DECA) ion, acquired during enzyme purification, residues in the gorge. There is additional electron density within the gorge that may represent small bound cations. When DECA and 2 cations are placed within the gorge, the simulation and the crystal structure are dramatically reconciled. The small cations, more so than DECA, appear to stabilize part of the gorge wall through electrostatic interactions. This part of the gorge wall is relatively thin and may regulate substrate, product, and water movement through the active site.
        )

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