Huperzine A Complexed with Acetylcholinesterase: Difference between revisions
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<StructureSection load='1vot' size='400' side='right' scene=' | <StructureSection load='1vot' size='400' side='right' scene='49/497129/Hup_in_ache/1' caption='Huperzine A complexed with AChE (PDP code [[1vot]])'> | ||
[[Image:1vot.jpg|left|200px]] | [[Image:1vot.jpg|left|200px]] | ||
'''3D Structure of Huperzine A Complexed with Acetylcholinesterase''' | '''3D Structure of Huperzine A Complexed with Acetylcholinesterase ([[1vot]])''' | ||
(see also [[AChE inhibitors and substrates (Part II)]]) | (see also [[AChE inhibitors and substrates (Part II)]]) | ||
==Background== | ==Background== | ||
<scene name='1vot/Huperzinea/2'>Huperzine A (HupA)</scene>, discovered by Chinese scientists from 1980s, has been proved to be a powerful, highly specific, and [http://en.wikipedia.org/wiki/Enzyme_inhibitor#Reversible_inhibitors reversible inhibitor] of [[acetylcholinesterase]] (AChE). It is a novel [http://en.wikipedia.org/wiki/Alkaloid alkaloid] originally isolated from the '''Traditional Chinese medicine''' [http://en.wikipedia.org/wiki/Traditional_Chinese_medicine] Qian Ceng Ta which is produced from the whole plant of the club moss [http://en.wikipedia.org/wiki/Huperzia_serrata ''Huperzia serrata'']. Qian Ceng Ta has been used for over 1000 years in China for treatment of [http://en.wikipedia.org/wiki/Bruise contusions], [http://en.wikipedia.org/wiki/Strain_(injury) strains], [http://en.wikipedia.org/wiki/Swelling_(medical) swellings], [http://en.wikipedia.org/wiki/Schizophrenia schizophrenia] and [http://en.wikipedia.org/wiki/Myasthenia_gravis myasthenia gravis]. Shuangyiping[http://www.54md.com/drugstore/pic/gpic_25fd25197010a0fb4a680516735e613c.jpg], a tablet form of HupA produced from the extracts of ''Huperzia serrata'', was developed in 1996 as a new drug for symptomatic treatment of Alzheimer’s disease in China. Compared with the other three [http://en.wikipedia.org/wiki/Food_and_Drug_Administration_(United_States) FDA]-approved drugs for the treatment of Alzheimer’s disease, Donepezil (Aricept, [[1eve]]), Rivastigmine (Exelon, [[1gqr]]), Galanthamine (Reminyl, [[1dx6]]), HupA has better penetration through the [http://en.wikipedia.org/wiki/Blood-brain_barrier blood-brain barrier], higher oral [http://en.wikipedia.org/wiki/Bioavailability bioavailability], and longer duration of AChE inhibitory action. | <scene name='1vot/Huperzinea/2'>Huperzine A (HupA)</scene>, discovered by Chinese scientists from 1980s, has been proved to be a powerful, highly specific, and [http://en.wikipedia.org/wiki/Enzyme_inhibitor#Reversible_inhibitors reversible inhibitor] of [[acetylcholinesterase]] (AChE). It is a novel [http://en.wikipedia.org/wiki/Alkaloid alkaloid] originally isolated from the '''Traditional Chinese medicine''' [http://en.wikipedia.org/wiki/Traditional_Chinese_medicine] Qian Ceng Ta which is produced from the whole plant of the club moss [http://en.wikipedia.org/wiki/Huperzia_serrata ''Huperzia serrata'']. [[Image:HuperzineA3.jpg|right|200px]] | ||
Qian Ceng Ta has been used for over 1000 years in China for treatment of [http://en.wikipedia.org/wiki/Bruise contusions], [http://en.wikipedia.org/wiki/Strain_(injury) strains], [http://en.wikipedia.org/wiki/Swelling_(medical) swellings], [http://en.wikipedia.org/wiki/Schizophrenia schizophrenia] and [http://en.wikipedia.org/wiki/Myasthenia_gravis myasthenia gravis]. Shuangyiping[http://www.54md.com/drugstore/pic/gpic_25fd25197010a0fb4a680516735e613c.jpg], a tablet form of HupA produced from the extracts of ''Huperzia serrata'', was developed in 1996 as a new drug for symptomatic treatment of Alzheimer’s disease in China. Compared with the other three [http://en.wikipedia.org/wiki/Food_and_Drug_Administration_(United_States) FDA]-approved drugs for the treatment of Alzheimer’s disease, Donepezil (Aricept, [[1eve]]), Rivastigmine (Exelon, [[1gqr]]), Galanthamine (Reminyl, [[1dx6]]), HupA has better penetration through the [http://en.wikipedia.org/wiki/Blood-brain_barrier blood-brain barrier], higher oral [http://en.wikipedia.org/wiki/Bioavailability bioavailability], and longer duration of AChE inhibitory action. | |||
The structure of HupA shows some similarity to other known [[AChE inhibitors and substrates]]. The molecule is fairly rigid and contains an [http://en.wikipedia.org/wiki/Aromaticity aromatic] system as well as a [http://en.wikipedia.org/wiki/Amine primary amino group] that is probably [http://en.wikipedia.org/wiki/Protonation protonated] at physiological [http://en.wikipedia.org/wiki/PH pH]. Various suggestions have been made with respect to its orientation within the active site of AChE, and with respect to the amino acid residue with which its putative [http://en.wikipedia.org/wiki/Pharmacophore pharmacophoric] groups might interact. Solution of the 3D structure of a complex of HupA with AChE would permit unequivocal resolution of this issue and it would also provide a rational basis for structure-related [http://en.wikipedia.org/wiki/Drug_design drug design] aimed at developing synthetic analogues of HupA with improved therapeutic properties. | The structure of HupA shows some similarity to other known [[AChE inhibitors and substrates]]. The molecule is fairly rigid and contains an [http://en.wikipedia.org/wiki/Aromaticity aromatic] system as well as a [http://en.wikipedia.org/wiki/Amine primary amino group] that is probably [http://en.wikipedia.org/wiki/Protonation protonated] at physiological [http://en.wikipedia.org/wiki/PH pH]. Various suggestions have been made with respect to its orientation within the active site of AChE, and with respect to the amino acid residue with which its putative [http://en.wikipedia.org/wiki/Pharmacophore pharmacophoric] groups might interact. Solution of the 3D structure of a complex of HupA with AChE would permit unequivocal resolution of this issue and it would also provide a rational basis for structure-related [http://en.wikipedia.org/wiki/Drug_design drug design] aimed at developing synthetic analogues of HupA with improved therapeutic properties. | ||
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For additional information, see: [[Alzheimer's Disease]] | For additional information, see: [[Alzheimer's Disease]] | ||
<br /> | <br /> | ||
</StructureSection> | |||
==Reference== | ==Reference== | ||
Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A., Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL, Nat. Struct. Biol. 1997 Jan;4(1):57-63. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8989325 8989325] | Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A., Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL, Nat. Struct. Biol. 1997 Jan;4(1):57-63. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8989325 8989325] | ||
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PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17644292 17644292] | PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17644292 17644292] | ||
[[zh:Huperzine_A_Complexed_with_Acetylcholinesterase (Chinese)]] | |||
[[en:Huperzine_A_Complexed_with_Acetylcholinesterase]] | |||
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[[Category: Acetylcholinesterase]] | [[Category: Acetylcholinesterase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||