Hydrogen exchange of the glycyl radical of pyruvate formate-lyase is catalyzed by cysteine 419 - PubMed (original) (raw)
. 1995 Feb 28;34(8):2393-9.
doi: 10.1021/bi00008a001.
Affiliations
- PMID: 7873518
- DOI: 10.1021/bi00008a001
Hydrogen exchange of the glycyl radical of pyruvate formate-lyase is catalyzed by cysteine 419
C V Parast et al. Biochemistry. 1995.
Abstract
Pyruvate formate-lyase (PFL) catalyzes the reversible conversion of CoA and pyruvate into acetyl-CoA and formate. Active enzyme contains a glycyl radical whose alpha-hydrogen undergoes rapid exchange with solvent (t1/2 approximately 5 min at 0 degree C). We have investigated this exchange using site-directed mutagenesis and mechanism-based inactivation. Mutation of the active-site cysteine 419 into a serine, which renders the enzyme catalytically inactive, abolishes alpha-hydrogen exchange in the radical. This suggests that the exchange process is not an intrinsic property of the glycyl radical but is a consequence of its interaction with cysteine 419. This residue is also demonstrated to be involved in the transfer of the radical to acetylphosphinate, a mechanism-based inactivator of the enzyme. In contrast, mutation of the other essential cysteine 418 to a serine has no effect on the hydrogen exchange or the transfer of the radical to acetylphosphinate. A mechanism for the hydrogen exchange catalyzed by cysteine 419 consistent with a redox role for this residue in the normal catalytic reaction is proposed.
Similar articles
- Inactivation of pyruvate formate-lyase by dioxygen: defining the mechanistic interplay of glycine 734 and cysteine 419 by rapid freeze-quench EPR.
Zhang W, Wong KK, Magliozzo RS, Kozarich JW. Zhang W, et al. Biochemistry. 2001 Apr 3;40(13):4123-30. doi: 10.1021/bi002589k. Biochemistry. 2001. PMID: 11300793 - Electron paramagnetic resonance evidence for a cysteine-based radical in pyruvate formate-lyase inactivated with mercaptopyruvate.
Parast CV, Wong KK, Kozarich JW, Peisach J, Magliozzo RS. Parast CV, et al. Biochemistry. 1995 May 2;34(17):5712-7. doi: 10.1021/bi00017a002. Biochemistry. 1995. PMID: 7727431 - Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase.
Becker A, Fritz-Wolf K, Kabsch W, Knappe J, Schultz S, Volker Wagner AF. Becker A, et al. Nat Struct Biol. 1999 Oct;6(10):969-75. doi: 10.1038/13341. Nat Struct Biol. 1999. PMID: 10504733 - Pyruvate formate-lyase mechanism involving the protein-based glycyl radical.
Knappe J, Elbert S, Frey M, Wagner AF. Knappe J, et al. Biochem Soc Trans. 1993 Aug;21 ( Pt 3)(3):731-4. doi: 10.1042/bst0210731. Biochem Soc Trans. 1993. PMID: 8135930 Review. No abstract available. - A glycyl radical solution: oxygen-dependent interconversion of pyruvate formate-lyase.
Sawers G, Watson G. Sawers G, et al. Mol Microbiol. 1998 Aug;29(4):945-54. doi: 10.1046/j.1365-2958.1998.00941.x. Mol Microbiol. 1998. PMID: 9767563 Review.
Cited by
- Discovery of a New Class of Aminoacyl Radical Enzymes Expands Nature's Known Radical Chemistry.
Fu B, Yang H, Kountz DJ, Lundahl MN, Beller HR, Broderick WE, Broderick JB, Hoffman BH, Balskus EP. Fu B, et al. J Am Chem Soc. 2024 Oct 30;146(43):29645-29655. doi: 10.1021/jacs.4c10348. Epub 2024 Oct 11. J Am Chem Soc. 2024. PMID: 39392720 Free PMC article. - Modeling the Initiation Phase of the Catalytic Cycle in the Glycyl-Radical Enzyme Benzylsuccinate Synthase.
Szaleniec M, Oleksy G, Sekuła A, Aleksić I, Pietras R, Sarewicz M, Krämer K, Pierik AJ, Heider J. Szaleniec M, et al. J Phys Chem B. 2024 Jun 20;128(24):5823-5839. doi: 10.1021/acs.jpcb.4c01237. Epub 2024 Jun 7. J Phys Chem B. 2024. PMID: 38848492 Free PMC article. - The Mechanism of Inhibition of Pyruvate Formate Lyase by Methacrylate.
Cáceres JC, Dolmatch A, Greene BL. Cáceres JC, et al. J Am Chem Soc. 2023 Oct 18;145(41):22504-22515. doi: 10.1021/jacs.3c07256. Epub 2023 Oct 5. J Am Chem Soc. 2023. PMID: 37797332 Free PMC article. - The Autonomous Glycyl Radical Protein GrcA Restores Activity to Inactive Full-Length Pyruvate Formate-Lyase In Vivo.
Kammel M, Sawers RG. Kammel M, et al. J Bacteriol. 2022 May 17;204(5):e0007022. doi: 10.1128/jb.00070-22. Epub 2022 Apr 4. J Bacteriol. 2022. PMID: 35377165 Free PMC article. - Thiyl Radical Reactions in the Chemical Degradation of Pharmaceutical Proteins.
Schöneich C. Schöneich C. Molecules. 2019 Nov 28;24(23):4357. doi: 10.3390/molecules24234357. Molecules. 2019. PMID: 31795282 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources