Irreversible inhibition of type I dehydroquinase by substrates for type II dehydroquinase

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 5, 2000, Pages 407-409

  Bello, Concepción González ^a   Harris, Joanna M ^a   Manthey, Michael K ^a   Coggins, John R ^b   Abell, Chris ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 DEHYDROQUINATE DEHYDRATASE; ENZYME INHIBITOR; QUINIC ACID; SHIKIMIC ACID DERIVATIVE;

ARTICLE; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; NONHUMAN;

ENZYME INHIBITORS; ESCHERICHIA COLI; HYDRO-LYASES; MYCOBACTERIUM TUBERCULOSIS; QUINIC ACID; SHIKIMIC ACID;

EID: 0013262319     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00057-3     Document Type: Article

References (14)

1. Abell, C. In Comprehensive Natural Products Chemistry, Sankawa, U., Ed., Elsevier: Amsterdam, 1999; p 573.
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3. Kleanthous C., Deka R., Davis K., Kelly S.M., Cooper A., Harding S.E., Price N.C., Hawkins A.R., Coggins J.R. Biochem. J. 282:1992;687.
4. Chaudhuri S., Lambert J.M., McColl L.A., Coggins J.R. Biochem. J. 239:1986;699.
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6. Shneier A., Kleanthous C., Deka R., Coggins J.R., Abell C. J. Am. Chem. Soc. 113:1991;9416.
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8. Haslam, E.; Turner, M. J.; Sargent, D.; Thompson, R. S. J. Chem. Soc. (C) 1971, 1489.
9. Turner, M. J.; Smith, B. W.; Haslam, E. J. Chem. Soc., Perkin Trans 1 1975, 52.
10. Harris J., Kleanthous C., Coggins J.R., Hawkins A.R., Abell C. J. Chem. Soc., Chem. Commun. 13:1993;1080.
11. Manthey, M. K.; González-Bello, C.; Abell, C. J. Chem. Soc., Perkin Trans 1 1997, 625.
12. González-Bello C., Manthey M.K., Harris J.H., Hawkins A.R., Coggins J.R., Abell C. J. Org. Chem. 63:1998;1591.
13. Type I dehydroquinase from E. coli was purified as in Duncan, K.; Chaudhuri, S.; Campbell, M. S.; Coggins, J. R. Biochem. J. 1986, 238, 475. Incubations of type I dehydroquinase (170 μg from a stock protein concentration of 21.5 mg/ml stored in 50% glycerol) with (2R)-2-bromo-3-dehydroquinic acid (3) (10 mM), (2R)-2-fluoro-3-dehydroquinic acid (5) (2.4 mM) and 2-bromo-3-dehydroshikimic acid (4) (10 mM) were carried out in phosphate buffer (100 mM for 3 and 4 and 50 mM for 5) at pH 7.0, 25 °C. Aliquots were removed and diluted into a standard assay mix containing 3-dehydroquinic acid (1) (500 μM for 3 and 4 and 560 μM for 5) in phosphate buffer (100 mM for 3 and 4 and 50 mM for 5) at pH 7.0, 25 °C. The formation of 3-dehydroshikimic acid (2) was monitored at 234 nm. Upon completion of the inhibition experiment, the protein samples were desalted with successive concentration and dilution using ammonium bicarbonate (4 mM) at 4 °C and in an Amicon Centricon-10 microconcentrator prior to loading on a electrospray mass spectrometer. Electrospray mass spectra were recorded on a VG BioQ quadrupole mass spectrometer.
14. Under the conditions of the enzyme incubation, but in the absence of enzyme, no decarboxylative loss of bromide or fluoride was observed from 3 or 5, respectively.