Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124

Proceedings of the National Academy of Sciences of the United States of America

Volumn 107, Issue 11, 2010, Pages 4878-4883

  Auld, Douglas S ^a   Lovell, Scott ^b   Thorne, Natasha ^a   Lea, Wendy A ^a   Maloney, David J ^a   Shen, Min ^a   Rai, Ganesha ^a   Battaile, Kevin P ^c   Thomas, Craig J ^a   Simeonov, Anton ^a   Hanzlik, Robert P ^b   Inglese, James ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b UNIVERSITY OF KANSAS   (United States)

^c ARGONNE NATIONAL LABORATORY   (United States)

Author keywords

Ataluren; Multisubstrate adduct inhibitor; Protein stability; Reporter gene assay; X ray crystallography

Indexed keywords

ATALUREN; FIREFLY LUCIFERASE;

ARTICLE; BINDING AFFINITY; CATALYSIS; CONTROLLED STUDY; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME BINDING; ENZYME INHIBITION; ENZYME STABILITY; ENZYME SUBSTRATE; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOLECULAR MODEL; PRIORITY JOURNAL; PROTEIN CONFORMATION;

ADENOSINE MONOPHOSPHATE; CELL LINE; COENZYME A; CRYSTALLOGRAPHY, X-RAY; ENZYME ASSAYS; ENZYME INHIBITORS; ENZYME STABILITY; HUMANS; ISOMERISM; LUCIFERASES, FIREFLY; MODELS, MOLECULAR; OXADIAZOLES; SOLUTIONS; SUBSTRATE SPECIFICITY; TEMPERATURE;

EID: 77950430317     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0909141107     Document Type: Article

References (31)

1. Fan F, Wood KV (2007) Bioluminescent assays for high-throughput screening. Assay Drug Dev Technol 5(1):127-136.
2. Roda A, Guardigli M, Michelini E, Mirasoli M (2009) Bioluminescence in analytical chemistry and in vivo imaging. TRAC-Trend Anal Chem 28(3):307-322.
3. Auld DS, et al. (2008) Characterization of chemical libraries for luciferase inhibitory activity. J Med Chem 51(8):2372-2386.
4. Heitman LH, et al. (2008) False positives in a reporter gene assay: Identification and synthesis of substituted N-pyridin-2-ylbenzamides as competitive inhibitors of firefly luciferase. J Med Chem 51(15):4724-4729.
5. Thompson JF, et al. (1997) Mutation of a protease-sensitive region in firefly luciferase alters light emission properties. J Biol Chem 272(30):18766-18771. (Pubitemid 27318223)
6. Thompson JF, Hayes LS, Lloyd DB (1991) Modulation of firefly luciferase stability and impact on studies of gene regulation. Gene 103(2):171-177.
7. Auld DS, Thorne N, Nguyen DT, Inglese J (2008) A specific mechanism for nonspecific activation in reporter-gene assays. ACS Chem Biol 3(8):463-470.
8. Auld DS, Thorne N, Maguire WF, Inglese J (2009) Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression. Proc Natl Acad Sci USA 106(9):3585-3590.
9. Welch EM, et al. (2007) PTC124 targets genetic disorders caused by nonsense mutations. Nature 447(7140):87-91.
10. Fersht AR, et al. (1985) Hydrogen bonding and biological specificity analysed by protein engineering. Nature 314(6008):235-238.
11. Jencks WP (1975) Binding energy, specificity, and enzymic catalysis: The Circe effect. Adv Enzymol Relat Areas Mol Biol 43:219-410.
12. Inglese J, Blatchly RA, Benkovic SJ (1989) A multisubstrate adduct inhibitor of a purine biosynthetic enzyme with a picomolar dissociation constant. J Med Chem 32(5):937-940.
13. Congreve M, Chessari G, Tisi D, Woodhead AJ (2008) Recent developments in fragment-based drug discovery. J Med Chem 51(13):3661-3680.
14. Korolev S, et al. (2002) The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor. Nat Struct Biol 9(1):27-31. (Pubitemid 34049175)
15. Inglese J, Benkovic SJ (1991) Multisubstrate adduct inhibitors of glycinamide ribonucleotide transformylase: Synthetic and enzyme-assembled. Tetrahedron 47(14-15):2351-2364.
16. Greasley SE, et al. (2001) Unexpected formation of an epoxide-derived multisubstrate adduct inhibitor on the active site of GAR transformylase. Biochemistry 40(45): 13538-13547.
17. Rhodes WC, McElroy WD (1958) The synthesis and function of luciferyl-adenylate and oxyluciferyl-adenylate. J Biol Chem 233(6):1528-1537.
18. Fraga H, Fernandes D, Fontes R, Esteves da Silva JC (2005) Coenzyme A affects firefly luciferase luminescence because it acts as a substrate and not as an allosteric effector. FEBS J 272(20):5206-5216. (Pubitemid 41503151)
19. Broom AD (1989) Rational design of enzyme inhibitors: Multisubstrate analogue inhibitors. J Med Chem 32(1):2-7.
20. Conti E, Franks NP, Brick P (1996) Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes. Structure 4(3):287-298. (Pubitemid 3036555)
21. Nakatsu T, et al. (2006) Structural basis for the spectral difference in luciferase bioluminescence. Nature 440(7082):372-376.
22. Branchini BR, Murtiashaw MH, Carmody JN, Mygatt EE, Southworth TL (2005) Synthesis of an N-acyl sulfamate analog of luciferyl-AMP: A stable and potent inhibitor of firefly luciferase. Bioorg Med Chem Lett 15(17):3860-3864.
23. 2 in a haloalkane dehalogenase. Proc Natl Acad Sci USA 100(5):2215-2219.
24. Ericsson UB, Hallberg BM, Detitta GT, Dekker N, Nordlund P (2006) Thermofluor-based high-throughput stability optimization of proteins for structural studies. Anal Biochem 357(2):289-298. (Pubitemid 44430091)
25. Parker J (1989) Errors and alternatives in reading the universal genetic code. Microbiol Rev 53(3):273-298.
26. Pace CN, Shirley BA, Thomson JA (1989) Measuring Conformational Stability of a Protein in Protein Structure (IRL, New York).
27. Thompson PA, et al. (2008) Identification of ligand binding by protein stabilization: Comparison of ATLAS with biophysical and enzymatic methods. Assay Drug Dev Techn 6(1):69-81.
28. Peltz SW, et al. (2009) Nonsense suppression activity of PTC124 (Ataluren). Proc Natl Acad Sci USA 106(25):E64 lett.
29. Inglese J, Thorne N, Auld DS (2009) Reply to Peltz et al: Post-translational stabilization of the firefly luciferase reporter by PTC124 (Ataluren). Proc Natl Acad Sci USA 106:E65 lett.
30. Wood KV (1995) The chemical mechanism and evolutionary development of beetle bioluminescence. Photochem Photobiol 62(4):662-673.
31. Lyssiotis CA, et al. (2009) Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proc Natl Acad Sci USA 106(22):8912-8917.