PMID: 8989325Jan 1, 1997Paper

Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A

Nature Structural Biology
M L RavesJ L Sussman

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.

References

Apr 30, 1992·Biochemical and Biophysical Research Communications·Y AshaniB P Doctor
Apr 15, 1991·Acta Crystallographica. Section C, Crystal Structure Communications·S J GeibA P Kozikowski
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Mar 1, 1990·Journal of Molecular Graphics·G Vriend
Mar 11, 1995·Lancet·K L Davis, P Powchik
Feb 1, 1995·Protein Engineering·A C WallaceJ M Thornton
Jun 1, 1995·Pharmacology, Biochemistry, and Behavior·Z Q Xiong, X C Tang
Dec 1, 1994·Journal of Computer-aided Molecular Design·Y P Pang, A P Kozikowski
Oct 1, 1994·Protein Science : a Publication of the Protein Society·A SaxenaB P Doctor
Aug 5, 1994·Journal of Molecular Biology·Z S DerewendaP M Kobos
Apr 1, 1993·Journal of Computer-aided Molecular Design·M L VerdonkJ Kroon
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M HarelJ L Sussman
Jan 23, 1987·Science·A T BrüngerM Karplus

❮ Previous
Next ❯

Citations

Jul 13, 2002·Journal of Computational Chemistry·Yuan-Ping PangFranklyn G. Prendergast
Sep 15, 2010·Journal of Molecular Modeling·Erica Cristina Moreno Nascimento, João B L Martins
Jul 28, 2007·Cellular and Molecular Neurobiology·Hai Yan ZhangXi Can Tang
Dec 18, 2004·Plant Molecular Biology·Samuel P FletcherTsafrir S Mor
Nov 6, 2003·Insect Biochemistry and Molecular Biology·Shizuo G KamitaBruce D Hammock
Dec 28, 1999·Biochemical Pharmacology·J Chang
Jun 19, 1998·Current Opinion in Structural Biology·J A McCammon
Nov 15, 2000·Bioorganic & Medicinal Chemistry Letters·V RajendranA P Kozikowski
Sep 12, 2001·Bioorganic & Medicinal Chemistry Letters·K HögenauerJ Mulzer
Dec 28, 1999·Bioorganic & Medicinal Chemistry Letters·F ZengR Ji
Jun 26, 1998·Journal of Molecular Graphics & Modelling·C E FelderJ L Sussman
Jun 20, 2013·Journal of Chemical Information and Modeling·Koteswara Rao ValasaniShirley Shidu Yan
Oct 6, 2012·Journal of Medicinal Chemistry·Jonah CheungJude J Height
May 14, 2009·The Journal of Physical Chemistry. B·Mihail Mihailescu, Hagai Meirovitch
Feb 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Dou YuYang D Teng
Feb 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Fang BaiHualiang Jiang
May 18, 2004·Natural Product Research·Dan StaerkJerzy W Jaroszewski
Sep 22, 2001·Protein Science : a Publication of the Protein Society·M WeikJ Kroon
Mar 30, 2000·Protein Science : a Publication of the Protein Society·I TsigelnyP Taylor
Jul 13, 2000·Protein Science : a Publication of the Protein Society·M HarelJ L Sussman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.