Mechanistic studies on phosphopantothenoylcysteine decarboxylase: Trapping of an enethiolate intermediate with a mechanism-based inactivating agent

Biochemistry

Volumn 43, Issue 49, 2004, Pages 15520-15533

  Strauss, Erick ^b   Zhai, Huili ^a   Brand, Leisl A ^b   McLafferty, Fred W ^a   Begley, Tadhg P ^a  

^a Department of Obstetrics Gynecology   (United States)

^b STELLENBOSCH UNIVERSITY   (South Africa)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDES; BIOSYNTHESIS; CATALYSIS; CHEMICAL BONDS; MUTAGENESIS; SUBSTRATES;

CYSTEINE MOIETY; DECARBOXYLATION; FLAVIN COFACTORS; PROTONATION;

ENZYMES;

4' PHOSPHO N (1 MERCAPTOMETHYLCYCLOPROPYL)PANTOTHENAMIDE; 4' PHOSPHOPANTOTHENOYLCYSTEINE; CARBOXYLYASE; COENZYME A; CYSTEINE DERIVATIVE; ENZYME INHIBITOR; FLAVOPROTEIN; ISOENZYME; PANTETHEINE PHOSPHATE; PHOSPHOPANTOTHENOYLCYSTEINE DECARBOXYLASE; SERINE; THIOALDEHYDE; THIOL DERIVATIVE; THREONINE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; COVALENT BOND; DECARBOXYLATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INACTIVATION; ENZYME KINETICS; ENZYME MECHANISM; ENZYME SYNTHESIS; ISOENZYME ANALYSIS; PRIORITY JOURNAL; PROTEIN FAMILY; PROTON TRANSPORT; SITE DIRECTED MUTAGENESIS;

BINDING SITES; CARBOXY-LYASES; CATALYSIS; CYSTEINE; DECARBOXYLATION; ENZYME INHIBITORS; ENZYME STABILITY; FLAVIN MONONUCLEOTIDE; HUMANS; KINETICS; MUTAGENESIS, SITE-DIRECTED; PANTETHEINE; PANTOTHENIC ACID; SERINE; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SUBSTRATE SPECIFICITY; SULFHYDRYL COMPOUNDS;

EID: 10644288567     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi048340a     Document Type: Article

References (46)

1. Begley, T. P., Kinsland, C., and Strauss, E. (2001) The biosynthesis of Coenzyme A in bacteria, Vitam. Horm. 61, 157-171.
2. Kupke, T., Hernandez-Acosta, P., Steinbacher, S., and Culianez-Macia, F. A. (2001) Arabidopsis thaliana flavoprotein AtHAL3a catalyzes the decarboxylation of 4′-phosphopantothenoylcysteine to 4′- phosphopantetheine, a key step in coenzyme A biosynthesis, J. Biol. Chem. 276, 19190-19196.
3. Daugherty, M., Polanuyer, B., Farrell, M., Scholle, M., Lykidis, A., De Crécy-Lagard, V., and Osterman, A. (2002) Complete Reconstitution of the Human Coenzyme A Biosynthetic Pathway via Comparitive Genomics, J. Biol. Chem. 277, 21431-21439.
4. Strauss, E., and Begley, T. P. (2001) Mechanistic Studies on Phosphopantothenoylcysteine Decarboxylase, J. Am. Chem. Soc. 123, 6449-6450.
5. Kupke, T., Uebele, M., Schmid, D., Jung, G., Blaesse, M., and Steinbacher, S. (2000) Molecular characterization of lantibiotic-synthesizing enzyme EpiD reveals a function for bacterial Dfp proteins in coenzyme A biosynthesis, J. Biol. Chem. 275, 31838-31846.
6. Strauss, E., and Begley, T. P. (2003) Stereochemical studies on phosphopantothenoylcysteine decarboxylase from Escherichia coli, Bioorg. Med. Chem. Lett. 13, 339-342.
7. Palfey, B. A., and Massey, V. (1998) Flavin-dependent Enzymes, in Comprehensive Biological Catalysis (Sinnott, M., Ed.) pp 83-154, Academic Press, San Diego, CA.
8. Miller, S. M., Massey, V., Ballou, D., Williams, C. H., Jr., Distefano, M. D., Moore, M. J., and Walsh, C. T. (1990) Use of a site-directed triple mutant to trap intermediates: demonstration that the flavin C(4a)-thiol adduct and reduced flavin are kinetically competent intermediates in mercuric ion reductase, Biochemistry 29, 2831-2841.
9. Thorpe, C., and Williams, C. H., Jr. (1981) Lipoamide dehydrogenase from pig heart. Pyridine nucleotide induced changes in monoalkylated two-electron reduced enzyme, Biochemistry 20, 1507-1513.
10. Kupke, T., Kempter, C., Jung, G., and Goetz, F. (1995) Oxidative decarboxylation of peptides catalyzed by flavoprotein EpiD. Determination of substrate specificity using peptide libraries and neutral loss mass spectrometry, J. Biol. Chem. 270, 11282-11289.
11. Kupke, T., Stevanovic, S., Sahl, H. G., and Goetz, F. (1992) Purification and characterization of EpiD, a flavoprotein involved in the biosynthesis of the lantibiotic epidermin, J. Bacteriol. 174, 5354-5361.
12. Majer, F., Schmid, D. G., Altena, K., Bierbaum, G., and Kupke, T. (2002) The flavoprotein MrsD catalyzes the oxidative decarboxylation reaction involved in formation of the peptidoglycan biosynthesis inhibitor mersacidin, J. Bacteriol. 184, 1234-1243.
13. Xie, L., and van der Donk, W. A. (2004) Post-translational modifications during lantibiotic biosynthesis, Curr. Opin. Chem. Biol. 8, 498-507.
14. Hernandez-Acosta, P., Schmid, D. G., Jung, G., Culianez-Macia, F. A., and Kupke, T. (2002) Molecular characterization of the Arabidopsis thaliana flavoprotein AtHAL3a reveals the general reaction mechanism of 4′-phosphopantothenoylcysteine decarboxylases, J. Biol. Chem. 277, 20490-20498.
15. Kupke, T. (2001) Molecular characterization of the 4′- phosphopantothenoylcysteine decarboxylase domain of bacterial Dfp flavoproteins, J. Biol. Chem. 276, 27597-27604.
16. Albert, A., Martinez-Ripoll, M., Espinosa-Ruiz, A., Yenush, L., Culianez-Macia, F. A., and Serrano, R. (2000) The X-ray structure of the FMN-binding protein AtHal3 provides the structural basis for the activity of a regulatory subunit involved in signal transduction, Structure 8, 961-969.
17. Blaesse, M., Kupke, T., Huber, R., and Steinbacher, S. (2000) Crystal structure of the peptidyl-cysteine decarboxylase EpiD complexed with a pentapeptide substrate, EMBO J. 19, 6299-6310.
18. Steinbacher, S., Hernandez-Acosta, P., Bieseler, B., Blaesse, M., Huber, R., Culianez-Macia, F. A., and Kupke, T. (2003) Crystal Structure of the Plant PPC Decarboxylase AtHAL3a Complexed with an Ene-thiol Reaction Intermediate, J. Mol. Biol. 327, 193-202.
19. Karthikeyan, S., Zhao, Z., Kao, C., Zhou, Q., Tao, Z., Zhang, H., and Liu, H.-w. (2004) Structural analysis of 1-aminocyclopropane-1-carboxylate deaminase: Observation of an aminyl intermediate and identification of Tyr294 as the active-site nucleophile, Angew. Chem., Int. Ed. 43, 3425-3429.
20. Zhao, Z., Chen, H., Li, K., Du, W., He, S., and Liu, H.-w. (2003) Reaction of 1-Amino-2-methylenecyclopropane-1-carboxylate with 1-Aminocyclopropane-1-carboxylate Deaminase: Analysis and Mechanistic Implications, Biochemistry 42, 2089-2103.
21. Liu, H.-W. (1998) Coenzyme B6 dependent novel bond cleavage reactions, Pure Appl. Chem. 70, 9-16.
22. 6, J. Am. Chem. Soc. 118, 8763-8764.
23. MacInnes, I., Nonhebel, D. C., Orszulik, S. T., Suckling, C. J., and Wrigglesworth, R. (1980) exo-Bicyclo[4.1.0]heptane-7-methanol: a novel latent inhibitor of liver alcohol dehydrogenase, J. Chem. Soc., Chem. Commun. 1068-1069.
24. MacInnes, I., Nonhebel, D. C., Orszulik, S. T., Suckling, C. J., and Wrigglesworth, R. (1983) Latent inhibitors. Part 3. The inhibition of lactate dehydrogenase and alcohol dehydrogenase by cyclopropane-containing compounds, J. Chem. Soc., Perkin Trans. 1, 2771-2776.
25. Ner, S. K., Suckling, C. J., Bell, A. R., and Wrigglesworth, R. (1987) Inhibition of carboxypeptidase by cyclopropane-containing peptides, J. Chem. Soc., Chem. Commun. 480-482.
26. Suckling, C. J. (1988) The cyclopropyl group in research on the mechanism and inhibition of enzymes, Angew. Chem., Int. Ed. Engl. 27, 537-552.
27. Haddow, J., Suckling, C. J., and Wood, H. C. S. (1989) Latent inhibitors. Part 5. Latent inhibition of dihydrofolate reductase by a pteridine-spiro- cyclopropane J. Chem. Soc., Perkin Trans. 1, 1297-1304.
28. Fraser, W., Suckling, C. J., and Wood, H. C. S. (1990) Latent inhibitors. Part 7. Inhibition of dihydroorotate dehydrogenase by spirocyclopropanobarbiturates, J. Chem. Soc., Perkin Trans. 1, 3137-3144.
29. McGill, J., Rees, L., Suckling, C. J., and Wood, H. C. S. (1992) Latent inhibitors. Part 8. Synthesis and evaluation of some mechanism-based inhibitors of dihydrofolate reductase, J. Chem. Soc., Perkin Trans. 1, 1299-1304.
30. Kemp, A., Ner, S. K., Rees, L., Suckling, C. J., Tedford, M. C., Bell, A. R., and Wrigglesworth, R. (1993) Latent inhibitors. Part 9. Substrate activated time-dependent inhibition of carboxypeptidase A by aminocyclopropanecarboxylic acid derivatives and analogs, J. Chem. Soc., Perkin Trans. 2, 741-748.
31. Silverman, R. B., Ding, C. Z., Borrillo, J. L., and Chang, J. T. (1993) Mechanism-based enzyme inactivation via a diactivated cyclopropane intermediate, J. Am. Chem. Soc. 115, 2982-2983.
32. Silverman, R. B., Lu, X., Blomquist, G. D., Ding, C. Z., and Yang, S. (1997) Inactivation of monoamine oxidase B by benzyl 1-(aminomethyl) cyclopropane-1-carboxylate, Bioorg. Med. Chem. 5, 297-304.
33. Danishefsky, S. (1979) Electrophilic cyclopropanes in organic synthesis, Acc. Chem. Res. 12, 66-72.
34. a value of the enethiol side chain is lower than that of the thiol side chain of peptides, J. Biol. Chem. 272, 4759-4762.
35. Moffatt, J. G., and Khorana, H. G. (1961) Nucleoside polyphosphates. XII. The total synthesis of coenzyme A, J. Am. Chem. Soc. 83, 663-675.
36. Strauss, E., Kinsland, C., Ge, Y., McLafferty, F. W., and Begley, T. P. (2001) Phosphopantothenoylcysteine synthetase from Escherichia coli. Identification and characterization of the last unidentified coenzyme A biosynthetic enzyme in bacteria, J. Biol. Chem. 276, 13513-13516.
37. O'Brien, W. E. (1976) A continuous spectrophotometric assay for argininosuccinate synthetase based on pyrophosphate formation, Anal. Biochem. 76, 423-430.
38. Strauss, E., and Begley, T. P. (2002) The Antibiotic Activity of N-Pentylpantothenamide Results from Its Conversion to Ethyldethia-Coenzyme A, a Coenzyme A Antimetabolite, J. Biol. Chem. 277, 48205-48209.
39. Wilm, M., and Mann, M. (1996) Analytical Properties of the Nanoelectrospray Ion Source, Anal. Chem. 68, 1-8.
40. Beu, S. C., Senko, M. W., Quinn, J. P., Wampler, F. M., III, and McLafferty, F. W. (1993) Fourier transform electrospray instrumentation for tandem high-resolution mass spectrometry of large molecules, J. Am. Soc. Mass Spectrom. 4, 557-565.
41. Horn, D. M., Zubarev, R. A., and McLafferty, F. W. (2000) Automated reduction and interpretation of high-resolution electrospray mass spectra of large molecules, J. Am. Soc. Mass Spectrom. 11, 320-332.
42. Sklenak, S., Apeloig, Y., and Rappoport, Z. (2000) Equilibria of simple thioenol/thiocarbonyl pairs. Comparison with the oxygen analogues and with the parent selenium and tellurium systems. A theoretical study J. Chem. Soc., Perkin Trans. 2, 2269-2279.
43. Kresge, A. J., and Meng, Q. (1998) 2,4,6-Trimethylthioacetophenone and Its Enol. The First Quantitative Characterization of a Simple Thiocarbonyl System in Aqueous Solution, J. Am. Chem. Soc. 120, 11830-11831.
44. 13C-labeled substrate, Angew. Chem., Int. Ed. Engl. 35, 2104-2107.
45. Manoj, N., and Ealick, S. E. (2003) Unusual space-group pseudosymmetry in crystals of human phosphopantothenoylcysteine decarboxylase, Acta Crystallogr., Sect. D: Biol. Crystallogr. 59, 1762-1766.
46. Silverman, R. B. (1995) Mechanism-based enzyme inactivators, Methods Enzymol. 249, 240-283.