A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo

Nature Chemical Biology

Volumn 4, Issue 8, 2008, Pages 483-490

  Yuzwa, Scott A ^a   Macauley, Matthew S ^a   Heinonen, Julia E ^a   Shan, Xiaoyang ^a   Dennis, Rebecca J ^b   He, Yuan ^b   Whitworth, Garrett E ^a   Stubbs, Keith A ^a   McEachern, Ernest J ^a   Davies, Gideon J ^b   Vocadlo, David J ^a  

^a SIMON FRASER UNIVERSITY   (Canada)

^b UNIVERSITY OF YORK   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; GLUCOSAMINE DERIVATIVE; O LINKED BETA N ACETYLGLUCOSAMINE; TAU PROTEIN; THIAMET G;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN; BRAIN CORTEX; CELL STRAIN; CONTROLLED STUDY; DRUG SYNTHESIS; HIPPOCAMPUS; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RAT;

RATTUS; VERTEBRATA;

EID: 47649114560     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.96     Document Type: Article

References (48)

1. Braak, H., Braak, E., Grundke-Iqbal, I. & Iqbal, K. Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci. Lett. 65, 351-355 (1986).
2. Lee, V.M., Goedert, M. & Trojanowski, J.Q. Neurodegenerative tauopathies. Annu. Rev. Neurosci. 24, 1121-1159 (2001).
3. Ksiezak-Reding, H., Liu, W.K. & Yen, S.H. Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments. Brain Res. 597, 209-219 (1992).
4. Schneider, A., Biernat, J., von Bergen, M., Mandelkow, E. & Mandelkow, E.M. Phosphorylation that detaches tau protein from microtubules (Ser262, Ser214) also protects it against aggregation into Alzheimer paired helical filaments. Biochemistry 38, 3549-3558 (1999).
5. Sengupta, A. et al. Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules. Arch. Biochem. Biophys. 357, 299-309 (1998).
6. Lindwall, G. & Cole, R.D. Phosphorylation affects the ability of tau protein to promote microtubule assembly. J. Biol. Chem. 259, 5301-5305 (1984).
7. Arnold, C.S. et al. The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine. J. Biol. Chem. 271, 28741-28744 (1996).
8. Liu, F., Iqbal, K., Grundke-Iqbal, I., Hart, G.W. & Gong, C.X. O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 101, 10804-10809 (2004).
9. Torres, C.R. & Hart, G.W. Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. J. Biol. Chem. 259, 3308-3317 (1984).
10. Cheng, X., Cole, R.N., Zaia, J. & Hart, G.W. Alternative O-glycosylation/O-phosphorylation of the murine estrogen receptor beta. Biochemistry 39, 11609-11620 (2000).
11. Chou, T.Y., Hart, G.W. & Dang, C.V. c-Myc is glycosylated at threonine 58, a known phosphorylation site and a mutational hot spot in lymphomas. J. Biol. Chem. 270, 18961-18965 (1995).
12. Comer, F.I. & Hart, G.W. Reciprocity between O-GlcNAc and O-phosphate on the carboxyl terminal domain of RNA polymerase II. Biochemistry 40, 7845-7852 (2001).
13. Zachara, N.E. & Hart, G.W. Cell signaling, the essential role of O-GlcNAc! Biochim. Biophys. Acta 1761, 599-617 (2006).
14. Kreppel, L.K., Blomberg, M.A. & Hart, G.W. Dynamic glycosylation of nuclear and cytosolic proteins. Cloning and characterization of a unique O-GlcNAc transferase with multiple tetratricopeptide repeats. J. Biol. Chem. 272, 9308-9315 (1997).
15. Lubas, W.A., Frank, D.W., Krause, M. & Hanover, J.A. O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats. J. Biol. Chem. 272, 9316-9324 (1997).
16. Dong, D.L. & Hart, G.W. Purification and characterization of an O-GlcNAc selective N-acetyl-β-D-glucosaminidase from rat spleen cytosol. J. Biol. Chem. 269, 19321-19330 (1994).
17. Gao, Y., Wells, L., Comer, F.I., Parker, G.J. & Hart, G.W. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic β-N-acetylglucosaminidase from human brain. J. Biol. Chem. 276, 9838-9845 (2001).
18. Lefebvre, T. et al. Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau proteins-a role in nuclear localization. Biochim. Biophys. Acta 1619, 167-176 (2003).
19. Li, X., Lu, F., Wang, J.Z. & Gong, C.X. Concurrent alterations of O-GlcNAcylation and phosphorylation of tau in mouse brains during fasting. Eur. J. Neurosci. 23, 2078-2086 (2006).
20. Farook, V.S., Bogardus, C. & Prochazka, M. Analysis of MGEA5 on 10q24.1-q24.3 encoding the β-O-linked N-acetylglucosaminidase as a candidate gene for type 2 diabetes mellitus in Pima Indians. Mol. Genet. Metab. 77, 189-193 (2002).
21. Le Corre, S. et al. An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic mice. Proc. Natl. Acad. Sci. USA 103, 9673-9678 (2006).
22. Engel, T., Goni-Oliver, P., Lucas, J.J., Avila, J. & Hernandez, F. Chronic lithium administration to FTDP-17 tau and GSK-3β overexpressing mice prevents tau hyper-phosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert. J. Neurochem. 99, 1445-1455 (2006).
23. Mazanetz, M.P. & Fischer, P.M. Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases. Nat. Rev. Drug Discov. 6, 464-479 (2007).
24. Macauley, M.S., Whitworth, G.E., Debowski, A.W., Chin, D. & Vocadlo, D.J. O-GlcNA-case uses substrate-assisted catalysis: kinetic analysis and development of highly selective mechanism-inspired inhibitors. J. Biol. Chem. 280, 25313-25322 (2005).
25. Dorfmueller, H.C. et al. GlcNAcstatin: a picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-GlcNAcylation levels. J. Am. Chem. Soc. 128, 16484-16485 (2006).
26. Kim, E.J., Perreira, M., Thomas, C.J. & Hanover, J.A. An O-GlcNAcase-specific inhibitor and substrate engineered by the extension of the N-acetyl moiety. J. Am. Chem. Soc. 128, 4234-4235 (2006).
27. Knapp, S. et al. Tautomeric modification of GlcNAc-thiazoline. Org. Lett. 9, 2321-2324 (2007).
28. Shanmugasundaram, B. et al. Inhibition of O-GlcNAcase by a gluco-configured nagstatin and a PUGNAc-imidazole hybrid inhibitor. Chem. Commun. (Camb.) 4372-4374 (2006).
29. Stubbs, K.A., Zhang, N. & Vocadlo, D.J. A divergent synthesis of 2-acyl derivatives of PUGNAc yields selective inhibitors of O-GlcNAcase. Org. Biomol. Chem. 4, 839-845 (2006).
30. Haltiwanger, R.S., Grove, K. & Philipsberg, G.A. Modulation of O-linked N-acetylglucosamine levels on nuclear and cytoplasmic proteins in vivo using the peptide O-GlcNAc-β-N-acetylglucosaminidase inhibitor O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate. J. Biol. Chem. 273, 3611-3617 (1998).
31. Horsch, M., Hoesch, L., Vasella, A. & Rast, D.M. N- acetylglucosaminono-1,5-lactone oxime and the corresponding (phenylcarbamoyl) oxime. Novel and potent inhibitors of β-N-acetylglucosaminidase. Eur. J. Biochem. 197, 815-818 (1991).
32. Scaffidi, A. et al. A 1-acetamido derivative of 6-epi-valienamine: an inhibitor of a diverse group of β-N-acetylglucosaminidases. Org. Biomol. Chem. 5, 3013-3019 (2007).
33. Zou, L. et al. The protective effects of PUGNAc on cardiac function after trauma-hemorrhage are mediated via increased protein O-GlcNAc levels. Shock 27, 402-408 (2007).
34. Macauley, M.S., Stubbs, K.A. & Vocadlo, D.J. O-GlcNAcase catalyzes cleavage of thioglycosides without general acid catalysis. J. Am. Chem. Soc. 127, 17202-17203 (2005).
35. Knapp, S. et al. NAG-thiazoline, An N-acetyl-β-hexosaminidase inhibitor that implicates acetamido participation. J. Am. Chem. Soc. 118, 6804-6805 (1996).
36. Whitworth, G.E. et al. Analysis of PUGNAc and NAG-thiazoline as transition state analogues for human O-GlcNAcase: mechanistic and structural insights into inhibitor selectivity and transition state poise. J. Am. Chem. Soc. 129, 635-644 (2007).
37. Cetinbas, N., Macauley, M.S., Stubbs, K.A., Drapala, R. & Vocadlo, D.J. Identification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. Biochemistry 45, 3835-3844 (2006).
38. Knapp, S., Kirk, B., Vocadlo, D. & Withers, S. An allosamizoline/glucosamine hybrid NAGase inhibitor. Synlett 1997, 435-436 (1997).
39. Terwisscha van Scheltinga, A.C. et al. Stereochemistry of chitin hydrolysis by a plant chitinase/lysozyme and X-ray structure of a complex with allosamidin: evidence for substrate assisted catalysis. Biochemistry 34, 15619-15623 (1995).
40. Dennis, R.J. et al. Structure and mechanism of a bacterial β-glucosaminidase having O-GlcNAcase activity. Nat. Struct. Mol. Biol. 13, 365-371 (2006).
41. Greene, L.A. & Tischler, A.S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc. Natl. Acad. Sci. USA 73, 2424-2428 (1976).
42. Comer, F.I., Vosseller, K., Wells, L., Accavitti, M.A. & Hart, G.W. Characterization of a mouse monoclonal antibody specific for O-linked N-acetylglucosamine. Anal. Biochem. 293, 169-177 (2001).
43. Li, T., Hawkes, C., Qureshi, H.Y., Kar, S. & Paudel, H.K. Cyclin-dependent protein kinase 5 primes microtubule-associated protein Tau site-specifically for glycogen synthase kinase 3β. Biochemistry 45, 3134-3145 (2006).
44. Cho, J.H. & Johnson, G.V. Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3β (GSK3β) plays a critical role in regulating tau's ability to bind and stabilize microtubules. J. Neurochem. 88, 349-358 (2004).
45. Kasai, K. & Yamaji, N. Novel chromogenic substrates for the rate-assay of N-acetyl-β-D-glucosaminidase-resorufinyl-N-acetyl and resazurinyl-N-acetyl-β-D-glucosaminides. Anal. Sci. 8, 161-164 (1992).
46. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50, 760-763 (1994).
47. Murshudov, G.N., Vagin, A.A. & Dodson, E.J. Refinement of macromolecular structures by the maximum likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240-255 (1997).
48. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (2004).