Formation and stability of a vinyl carbanion at the active site of orotidine 5′-monophosphate decarboxylase: pKa of the C-6 proton of enzyme-bound UMP

Journal of the American Chemical Society

Volumn 130, Issue 5, 2008, Pages 1574-1575

  Amyes, Tina L ^a   Wood, Bryant M ^b   Chan, Kui ^b   Gerlt, John A ^b   Richard, John P ^a  

^a UNIVERSITY AT BUFFALO   (United States)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTIC ACID; DEUTERIUM; LYSINE; OROTIDINE 5' PHOSPHATE DECARBOXYLASE; PROTON; UNCLASSIFIED DRUG; URIDINE PHOSPHATE; VINYL CARBANION; VINYL DERIVATIVE;

ARTICLE; CATALYSIS; CATALYST; DECARBOXYLATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; HYDROGEN BOND; PKA; PROTON NUCLEAR MAGNETIC RESONANCE; PROTON TRANSPORT; REACTION ANALYSIS; REACTION TIME; SACCHAROMYCES CEREVISIAE;

BINDING SITES; CARBON; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR STRUCTURE; OROTIDINE-5'-PHOSPHATE DECARBOXYLASE; PROTEIN BINDING; PROTONS; URIDINE MONOPHOSPHATE; VINYL COMPOUNDS;

EID: 38949172353     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja710384t     Document Type: Article

References (18)

1. Miller, B. G.; Wolfenden, R. Annu. Rev. Biochem. 2002, 71, 847-885.
2. Miller, B. G.; Hassell, A. M.; Wolfenden, R.; Milburn, M. V.; Short, S. A. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 2011-2016.
3. Appleby, T. C.; Kinsland, C.; Begley, T. P.; Ealick, S. E. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 2005-2010.
4. Toth, K.; Amyes, T. L.; Wood, B. M.; Chan, K.; Gerlt, J. A.; Richard, J. P. J. Am. Chem. Soc. 2007, 129, 12946-12947.
5. Radzicka, A.; Wolfenden, R. Science 1995, 267, 90-93.
6. Jencks, W. P. Adv. Enzymol. Relat. Areas Mol. Biol. 1975, 43, 219-410.
7. Wu, N.; Mo, Y.; Gao, J.; Pai, E. F. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 2017-2022.
8. Gao, J. Curr. Opin. Struct. Biol. 2003, 13, 184-192.
9. Warshel, A.; Strajbl, M.; Villa, J.; Florian, J. Biochemistry 2000, 39, 14728-14738.
10. Callahan, B. P.; Wolfenden, R. J. Am. Chem. Soc. 2004, 126, 14698-14699.
11. The reported failure to detect deuterium exchange in an earlier study is likely due to the use of only a small amount of enzyme and a relatively short reaction time: Smiley, J. A.; DelFraino, B. J.; Simpson, B. A. Arch. Biochem. Biophys. 2003, 412, 267-271.
12. The exchange reaction does not occur in the presence of a saturating amount of the competitive inhibitor 6-aza-uridine 5′-monophosphate.
13. a = 8.8: Porter, D. J. T.; Short, S. A. Biochemistry 2000, 39, 11788-11800.
14. -1 for unhindered rotation within an ion pair in water: Richard, J. P.; Tsuji, Y. J. Am. Chem. Soc. 2000, 122, 3963-3964.
15. We have observed that deuterium exchange into UMP is also catalyzed by the OMPDCs from Methanobacterium thermoautotrophicum and Escherichia coli.
16. Sievers, A.; Wolfenden, R. J. Am. Chem. Soc. 2002, 124, 13986-13987.
17. Wong, F. M.; Capule, C. C.; Wu, W. Org. Lett. 2006, 8, 6019-6022.
18. Yeoh, F. Y.; Cuasito, R. R.; Capule, C. C.; Wong, F. M.; Wu, W. Bioorg. Chem. 2007, 35, 338-343.