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

Nature Structural Biology

Volumn 4, Issue 1, 1997, Pages 57-63

  Raves, Mia L ^a   Harel, Michal ^a   Pang, Yuan Ping ^b   Silman, Israel ^a   Kozikowski, Alan P ^c   Sussman, Joel L ^a,d  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b MAYO CLINIC   (United States)

^c GEORGETOWN UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d BROOKHAVEN NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINESTERASE; ALKALOID; CHINESE DRUG; CHOLINESTERASE INHIBITOR; DRUG CARRIER; HUPERZINE A; NOOTROPIC AGENT;

ARTICLE; BINDING AFFINITY; CHINESE MEDICINE; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME INHIBITOR COMPLEX; ENZYME STRUCTURE; HYDROPHOBICITY; LIGAND BINDING; PRIORITY JOURNAL; TRADITIONAL MEDICINE;

ACETYLCHOLINESTERASE; CRYSTALLOGRAPHY, X-RAY; NOOTROPIC AGENTS; PROTEIN BINDING; PROTEIN CONFORMATION; SESQUITERPENES;

BRYOPHYTA; LYCOPODIUM;

EID: 0031015343     PISSN: 10728368     EISSN: None     Source Type: Journal    
DOI: 10.1038/nsb0197-57     Document Type: Article

References (45)

1. Liu, J.-S. et al. The structures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity. Can. J. Chem. 64, 837-839 (1986).
2. Wang, Y.E., Yue, D.X. & Tang, X.C. Anticholinesterase activity of huperzine A. Acta Pharmacol. Sinica 7, 110-113 (1986).
3. Kozikowski, A.P., Thiels, E., Tang, X.-C. & Hanin, I. Huperzine A - A possible lead structure in the treatment of Alzheimer's disease. Adv. Med. Chem. 1, 175-205 (1992).
4. Tang, X.C., Xiong, Z.Q., Qian, B.C., Zhou, Z.F. & Zhang, C.L. Cognition improvement by oral Huperzine A: a novel acetylcholinesterase inhibitor, in Alzheimer Disease: Therapeutic Strategies (eds E. Giacobini & R. Becker) 113-119 (Birkhäuser, Boston, 1994).
5. Dunnett, S.B. & Fibiger, H.C. Role of forebrain cholinergic systems in learning and memory: relevance to the cognitive deficits of aging and Alzheimer's dementia. Prog. Brain Res. 98, 413-420 (1993).
6. Becker, R.E. & Giacobini, E. Cholinergic Basis for Alzheimer Therapy (Birkhäuser, Boston, 1991).
7. Davis, K.L. & Powchik, P. Tacrine. Lancet 345, 625-630 (1995).
8. Giacobini, E. & Becker, R. Alzheimer Disease: Therapeutic Strategies (Birkhäuser, Boston, 1994).
9. Laganière, S., Corey, J., Tang, X.-C., Wülfert, E. & Hanin, I. Acute and chronic studies with the anticholinesterase huperzine A: Effect on central nervous system cholinergic parameters. Neuropharmacology 30, 763-768 (1991).
10. Xiong, Z.Q. & Tang, X.C. Effect of Huperzine A, a novel acetylcholinesterase inihibitor, on radial maze performance in rats. Pharmacol. Biochem. Behavior 51, 415-419 (1995).
11. Zhang, R.W. et al. Drug evaluation of huperzine A in the treatment of senile memory disorders. Acta Pharmacol. Sinica 12, 250-252 (1991).
12. Ved, H.S., Koenig, M.L., Dave, J.R. & Doctor, B.P. Huperzine A decreases neuronal cell death caused by glutamate. Neurobiol. Aging, submitted.
13. Geib, S.J., Tückmantel, W. & Kozikowski, A.P. Huperzine A - a potent acetylcholinesterase inhibitor of use in the treatment of Alzheimer's disease. Acta Crystallogr. 47, 824-827 (1991).
14. Ashani, Y., Grunwald, J., Kronman, C., Velan, B. & Shafferman, A. Role of tyrosine 337 in the binding of huperzine A to the active site of human acetylcholinesterase. Mol. Pharmacol. 45, 555-560 (1994).
15. McKinney, M., Miller, J.H., Yamada, F., Tückmantel, W. & Kozikowski, A.P. Potencies and stereoselectvities of enantiomers of huperzine A for inhibition of rat cortical acetylcholinesterase. Eur. J. Pharmacol. 203, 303-305 (1991).
16. Saxena, A. et al. Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases. Prot. Sci. 3, 1770-1778 (1994).
17. Pang, Y.-P. & Kozikowski, A. Prediction of the binding sites of huperzine A in acetylcholinesterase by docking studies. J. Computer-Aided Mol. Design 8, 669-681 (1994).
18. Sussman, J.L. et al. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 253, 872-879 (1991).
19. Harel, M. et al. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Prac. Natl. Acad. Sci. USA 90, 9031-9035 (1993).
20. Axelsen, P.H., Harel, M., Silman, I. & Sussman, J.L. Structure and dynamics of the active site gorge of acetylcholinesterase: synergistic use of molecular dynamics simulation and X-ray crystallography. Prot. Sci. 3, 188-197 (1994).
21. Harel, M., Quinn, D.M., Nair, H.K., Silman, I. & Sussman, J.L. The X-ray structure of a transition state analog complex reveals the molecular origins of the catalytic power and substrate specificity of acetylcholinesterase. J. Am. Chem. Soc. 118, 2340-2346 (1996).
22. Wlodek, S.T. et al. in Enzymes of the cholinesterase family (eds. Balasubramanian, A.L., Doctor, B.P., Taylor, P. & Quinn, D.M.) 97-104 (Plenum Press, New York, 1995).
23. Dougherty, D.A. Cation-π interactions in chemistry and biology: a new view of benzene, Phe, Tyr and Trp. Science 271, 163-168 (1996).
24. Kozikowski, A.P. et al. Synthesis of huperzine A and its analogues and their anticholinesterase activity. J. Org. Chem. 56, 4636-4645 (1991).
25. Verdonk, M.L., Boks, G.J., Kooijman, H., Kanters, J.A. & Kroon, J. Stereochemistry of charged nitrogen-aromatic interactions and its involvement in ligand-receptor binding. J. Computer-Aided Mol. Design 7, 173-182 (1993).
26. Sussman, J.L., Seeman, N.C., Kim, S.-H. & Berman, H.M. The crystal structure of a naturally occurring dinucleotide phosphate uridylyl 3′,5′-adenosine phosphate. models for RNA chain folding. J. Mol. Biol. 66, 403-421 (1972).
27. Taylor, R. & Kennard, O. Crystallographic evidence for the existence of C-H...O, C-H....N, and C-H...Cl hydrogen bonds. J. Am. Chem. Soc. 104, 5063-5070 (1982).
28. Derewenda, Z.S., Derewenda, U. & Kobos, P.M. (His) C-H...O=C< hydrogen bond in the active sites of serine hydrolases. J. Mol. Biol. 241, 83-93 (1994).
29. Kozikowski, A.P. et al. Identification of a more potent analogue of the naturally occurring alkaloid Huperzine A; predictive molecular modeling of its interaction with AChE. J. Am. Chem. Soc. 118, 11357-11362 (1996).
30. Harel, M., Kleywegt, G.J., Ravelli, R.B.G., Silman, I. & Sussman, J.L. Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target. Structure 3, 1355-1366 (1995).
31. Jones, T.A., Zou, J.-Y., Cowan, S.W. & Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A47, 110-119 (1991).
32. Ashani, Y., Peggins III, J.O. & Doctor, B.P. Mechanism of inhibition of cholinesterases by huperzine A. Biochem. Biophys. Res. Comm. 184, 719-726 (1992).
33. Sussman, J.L. et al. Purification and crystallization of a dimeric form of acetylcholinesterase from Torpedo california subsequent to solubilization with phosphatidylinositol-specific phospholipase C. J. Mol. Biol. 203, 821-823 (1988).
34. McPherson, A. The growth and preliminary investigation of protein and nucleic acid crystals for X-ray diffraction analysis. Meth. Biochem. Anal. 23, 249-345 (1976).
35. Otwinowski, Z. Oscillation data reduction program, in Data Collection and Processing, Proceedings of the CCP4 Study Weekend 29-30 January 1993 (eds L. Sawyer, N. Isaacs & S. Bailey) 56-62 (SERC, Daresbury, 1993).
36. Brünger, A.T., Kuriyan, J. & Karplus, M. Crystallographic R factor refinement by molecular dynamics. Science 235, 458-460 (1987).
37. Engh, R.H. & Huber, R. Accurate bond and angle parameters for X-ray protein structure refinement. J. Appl. Crystallogr. A47, 392-400 (1991).
38. Laskowski, R.A., MacArthur, M.W., Moss, D. & Thornton, J.M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26, 283-291 (1993).
39. Vriend, G. WHAT IF: a molecular modelling and drug design program J. Mol. Graph. 8, 52-56 (1990).
40. Kleywegt, G.J. & Jones, T.A. Efficient rebuilding of protein structures. Acta Crystallogr. D52, 829-832 (1996).
41. lnsightll v. 2.3.0, (Biosym Technologies, San Diego, 1993)
42. Wallace, A.C., Laskowski, R.A. & Thornton, J.M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Engng. 8, 127-134 (1995).
43. Kozikowski, A.P., Yamada, F., Tang, X.-C. & Hanin, I. Synthesis and biological evaluation of (+/-)-Z-huperzine A. Tetrahedr. Let. 31, 6159-6162 (1990).
44. Kozikowski, A.P. et al. Delineating the pharmacophoric elements of huperzine A: importance of the unsaturated three-carbon bridge to its AChE inhibitory activity. J. Med. Chem. 34, 3399-3402 (1991).
45. Liu, J.-S. & Huang, M.-F. The alkaloids huperzines C and D and huperzinine from Lycopodiastrum casuarinoides. Phytochemistry 37, 1759-1761 (1994).