Skip to main content

Suicide Substrates: Mechanism-Based Inactivators of Specific Target Enzymes

  • Chapter
Chemical Recognition in Biology

Part of the book series: Molecular Biology, Biochemistry and Biophysics ((MOLECULAR,volume 32))

Abstract

It is a great pleasure to present this paper at a symposium celebrating the 80th birthday of Professor Fritz Lipmann both because of my personal association with him (admittedly stretching back only a mere 15 years) and because he is such a seminal figure in the development of biochemistry and enzymology. I joined the Lipmann laboratory in 1965 as a graduate student to do my doctoral research with Len Spector and initiated mechanistic studies on how citrate was cleaved to acetyl CoA and oxalacetate by the cytoplasmic citrate cleavage enzyme (ATP citrate lyase), discovered by Lipmann and Srere some years earlier in 1953 (Srere and Lipmann 1953). Although (or perhaps because) most other people in the Lipmann laboratory were working on protein biosynthesis, Dr. Lipmann always evinced a lively interest in my experiments and other enzymatic mechanistic studies. Perhaps as a result, I had the pleasure of reading through the autobiographical manuscript of his which became his book Wanderings of a Biochemist (Lipmann 1971). That experience increased my appreciation for the breadth of contributions to biochemistry made by the central figure of this meeting.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bloch K (1969) Enzymatic synthesis of monounsaturated fatty acids. Acc Chem Res 2: 193

    Article  CAS  Google Scholar 

  • Bloch K (1972) In: Boyer P (ed) The enzymes, 3rd ed, vol V, p 441. Academic Press, New York

    Google Scholar 

  • Fisher J, Knowles J (1978) Bacterial resistance to β-lactams: The β-lactamases. In: Clarke FH (ed) Annual reports of medicinal chemistry, vol XIII, p 239. Academic Press, New York

    Google Scholar 

  • Fisher J, Charnas R, Knowles J (1978) Kinetic studies on the inactivation of E. coli RTEM β-lacta-mase by clavulanic acid. Chemical studies on the inactivation of E. coli RTEM β-lactamase by clavulanic acid. Biochemistry 17: 2180, 2185

    PubMed  Google Scholar 

  • Johnston M, Jankowski D, Marcotte P, Soda K, Walsh C (1979) Suicide inactivation of bacterial cystathionine γ-synthetase and methionine γ-lyase during processing of L-propargylglycine. Biochemistry 18: 1729

    Article  PubMed  CAS  Google Scholar 

  • Kollonitsch J, Barash L (1976) Organofluorine synthesis via photofluorination: 3-fluoro-D-alanine and 2-deuterio analogue, antibacterials related to the bacterial cell wall. J Am Chem Soc 98: 5591

    Article  PubMed  CAS  Google Scholar 

  • Kollonitsch J, Barash L, Kahan F, Kropp H (1973) New antibacterial agent via photofluorination of a bacterial cell wall constituent. Nature 243: 346

    Article  PubMed  CAS  Google Scholar 

  • Kollonitsch J, Patchett A, Marburg S, Maycock A, Perkins L, Doldouras G, Duggan D, Aster S (1978) Selective inhibitors of biosynthesis of aminergic neurotransmitters. Nature 274: 906

    Article  PubMed  CAS  Google Scholar 

  • Lipmann F (1971) Wanderings of a biochemist. Wiley, New York

    Google Scholar 

  • Marcotte P, Walsh C (1975) Active site-directed inactivation of cystathionine γ-synthetase and glutamic pyruvic transaminase by propargylglycine. Biochem Biophys Res Commun 62: 677

    Article  PubMed  CAS  Google Scholar 

  • Marcotte P, Walsh C (1978) Properties of D-amino acid oxidase covalently modified upon its oxidation of D-propargylglycine. Biochemistry 17: 2864

    Article  PubMed  CAS  Google Scholar 

  • Maycock A, Abeles R (1976) Suicide enzyme inactivators. Acc Chem Res 9:313

    Article  Google Scholar 

  • Maycock A, Abeles R, Salach J, Singer T (1976) The structure of the covalent adduct formed by the interaction of 3-dimethylamino-l-propyne and the flavine of mitochondrial amine oxidase. Biochemistry 15: 114

    Article  PubMed  CAS  Google Scholar 

  • Mishima H, Kurihara H, Kobayashi K, Miyazawa S, Terahara A (1976) γ-aminobutyrate aminotransferase inhibitor of microbial origin (enzyme inhibitor; cyclohexa-1,3-diene amino acid). Tetrahedron Lett 7: 537

    Google Scholar 

  • Ortiz de Montellano PR, Vinson W (1979) Carboxylic and phosphate esters of α-fluoro alcohols. J Am Chem Soc 101: 2222

    Article  CAS  Google Scholar 

  • Ortiz de Montellano PR, Mico BA, Yost GS, Correra MA (1978) Suicidal inactivation of cytochrome P-450: Covalent binding of allylisopropylacetamide to the heme prosthetic groups. p 337 in: see ref. Seiler et al. 1978

    Google Scholar 

  • Palfreyman MG, Danzin C, Jung MJ, Fozard JR, Wagner J, Woodward JK, Aubry M, Dage RC, Koch-Weser J (1978) Substrate-induced irreversible inhibition of aromatic L-amino acid decarboxylase by α-difluoromethyl-DOPA. p 221 in: see ref. Seiler et al. 1978

    Google Scholar 

  • Pogolotti AL Jr, Santi DV (1977) The catalytic mechanism of thymidylate synthetase. In: van Tamelen (ed) Bioorganic chemistry, vol 1, Enzyme action, p 277. Academic Press, New York

    Google Scholar 

  • Rando R (1974) Chemistry and enzymology of kcat inhibitors. Science 185: 320

    Article  PubMed  CAS  Google Scholar 

  • Rando R (1975) Mechanisms of action of naturally occurring irreversible enzyme inhibitors. Acc Chem Res 8: 281

    Article  CAS  Google Scholar 

  • Rando R (1978) Principles of catalytic enzyme inhibition, p 13 in: see ref. Seiler et al. 1978

    Google Scholar 

  • Santi DV, Wataya Y, Matsuda A (1978) Approaches to the design of mechanism-based inhibitors of pyrimidine metabolism. p 291 in: see ref. Seiler et al. 1978

    Google Scholar 

  • Scannell J, Preuss D, Demny T, Weiss F, Williams J, Stempel A (1971) Antimetabolites produced by microorganisms. II L-2-amino-4-pentynoic acid. J Antibiot 24: 239

    PubMed  CAS  Google Scholar 

  • Seiler N, Jung MJ, Koch-Weser J (eds) (1978) Enzyme-activated irreversible inhibitors. Elsevier/North-Holland, New York

    Google Scholar 

  • Shaw E (1970) Chemical modification by active-site-directed reagents. In: Boyer P (ed) The enzymes, 3rd ed, vol I, p 91. Academic Press, New York

    Google Scholar 

  • Silverman R (1979) In: Kaiman T (ed) Medicinal chemistry VI. Elsevier/North-Holland, New York (in press)

    Google Scholar 

  • Silverman R, Abeles R (1976) Inactivation of pyridoxal phosphate dependent enzymes by mono-and polyhaloalanines. Biochemistry 15: 4718

    Article  PubMed  CAS  Google Scholar 

  • Silverman R, Abeles R (1977) Mechanism of inactivation of γ-eystathionase by β,β,β-trifluoroalanine. Biochemistry 16: 5515

    Article  PubMed  CAS  Google Scholar 

  • Srere P, Lipmann F (1953) An enzymatic reaction between citrate, adenosine triphosphate and coenzyme A. J Am Chem Soc 75: 4874

    Article  CAS  Google Scholar 

  • Walsh C (1977) Recent developments in suicide substrates and other active site-directed inactivating agents of specific target enzymes. In: Horizons in biochemistry and biophysics, vol III, p 36. Addison-Wesley, Reading, MA

    Google Scholar 

  • Walsh C (1978) Chemical approaches to the study of enzymes catalyzing redox transformations. Ann Rev Biochem 47: 881

    Article  PubMed  CAS  Google Scholar 

  • Walsh C (1979) Enzymatic reaction mechanisms (see Chapter 4). Freeman, San Francisco

    Google Scholar 

  • Walsh C, Abeles R (1973) Acetylenic enzyme inhibitors. Inactivation of γ-cystathionase, in vitro and in vivo, by propargylglycine. J Am Chem Soc 95: 6125

    Article  Google Scholar 

  • Walsh C, Johnston M, Marcotte P, Wang E (1978) Studies on suicide substrates for pyridoxal-P linked enzymes. p 177 in: see ref Seiler et al. 1978

    Google Scholar 

  • Wang E (1979) Mechanistic studies on alanine racemase and serine transhydroxymethylase. PhD diss, Biol Dep. M.I.T.

    Google Scholar 

  • Wang E, Walsh C (1978) Suicide substrates for the alanine racemase of E. coli B. Biochemistry 17: 1313

    Article  PubMed  CAS  Google Scholar 

  • Wang E, Kallen R, Walsh C (1979) D-fluoroalanine: A suicide sub strate for serine transhydroxymethylase. In: Kisluik R, Brown G (eds) Chemistry and biology of pteridines, p 507. Elsevier/North-Holland, New York

    Google Scholar 

  • Wiseman J, Abeles R (1979) Mechanism of inhibition of aldehyde dehydrogenase by cyclopropanone hydrate and the mushroom toxin coprine. Biochemistry 18: 427

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1980 Springer-Verlag Berlin · Heidelberg

About this chapter

Cite this chapter

Walsh, C. (1980). Suicide Substrates: Mechanism-Based Inactivators of Specific Target Enzymes. In: Chapeville, F., Haenni, AL. (eds) Chemical Recognition in Biology. Molecular Biology, Biochemistry and Biophysics, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81503-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-81503-4_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-81505-8

  • Online ISBN: 978-3-642-81503-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics