PDBsum entry 1vot

Hydrolase

PDB id: 1vot

Contents

Protein chain

529 a.a.

Ligands

HUP

Waters ×208

References listed in PDB file

Key reference

• Title: Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-Huperzine a.
• Authors: M.L.Raves, M.Harel, Y.P.Pang, I.Silman, A.P.Kozikowski, J.L.Sussman.
• Ref.: Nat Struct Biol, 1997, 4, 57-63.
• PubMed id: 8989325

Abstract

(-)-Huperzine A (HupA) is found in an extract from a club moss that has been used for centuries in Chinese folk medicine. Its action has been attributed to its ability to strongly inhibit acetylcholinesterase (AChE). The crystal structure of the complex of AChE with optically pure HupA at 2.5 A resolution shows an unexpected orientation for the inhibitor with surprisingly few strong direct interactions with protein residues to explain its high affinity. This structure is compared to the native structure of AChE devoid of any inhibitor as determined to the same resolution. An analysis of the affinities of structural analogues of HupA, correlated with their interactions with the protein, shows the importance of individual hydrophobic interactions between HupA and aromatic residues in the active-site gorge of AChE.

Secondary reference #1

• Title: Mechanism of inhibition of cholinesterases by huperzine a.
• Authors: Y.Ashani, J.O.Peggins, B.P.Doctor.
• Ref.: Biochem Biophys Res Commun, 1992, 184, 719-726.
• PubMed id: 1575745

Secondary reference #2

• Title: Huperzine a--A potent acetylcholinesterase inhibitor of use in the treatment of alzheimer'S disease.
• Authors: S.J.Geib, W.Tückmantel, A.P.Kozikowski.
• Ref.: Acta Crystallogr C, 1991, 47, 824-827.
• PubMed id: 1863425

Secondary reference #3

• Title: Atomic structure of acetylcholinesterase from torpedo californica: a prototypic acetylcholine-Binding protein.
• Authors: J.L.Sussman, M.Harel, F.Frolow, C.Oefner, A.Goldman, L.Toker, I.Silman.
• Ref.: Science, 1991, 253, 872-879. [DOI no: 10.1126/science.1678899]
• PubMed id: 1678899