PMID: 8939706Nov 1, 1996Paper

Biochemical characterization of peptidyl carrier protein (PCP), the thiolation domain of multifunctional peptide synthetases

Chemistry & Biology
T StachelhausM A Marahiel

Abstract

A structurally diverse group of bioactive peptides is synthesized by peptide synthetases which act as templates for a growing peptide chain, attached to the enzyme via a thioester bond. The protein templates are composed of distinctive substrate-activating modules, whose order dictates the primary structure of the corresponding peptide product. Each module contains defined domains that catalyze adenylation, thioester and peptide bond formation, as well as substrate modifications. To show that a putative thiolation domain (PCP) is involved in covalent binding and transfer of amino acyl residues during non-ribosomal peptide synthesis, we have cloned and biochemically characterized that region of tyrocidine synthetase 1, TycA. The 327-bp gene fragment encoding PCP was cloned using its homology to the genes for the acyl carrier proteins of fatty acid and polyketide biosynthesis. The protein was expressed as a His6 fusion protein, and purified in a single step by affinity chromatography. Incorporation of beta-[3H]alanine, a precursor of coenzyme A, demonstrated the modification of PCP with the cofactor 4'-phosphopantetheine. When an adenylation domain is present to supply the amino adenylate moiety, PCP can be acylated in vitro. PCP...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jul 27, 1992·FEBS Letters·M A Marahiel
Jan 1, 1990·Annual Review of Genetics·D A Hopwood, D H Sherman
Jan 1, 1985·Molecular & General Genetics : MGG·M A MarahielH J Skarpeid
Jul 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·D DiMaioT Maniatis
Mar 17, 1995·The Journal of Biological Chemistry·T Stachelhaus, M A Marahiel
Oct 20, 1995·The Journal of Biological Chemistry·R H Lambalot, C T Walsh
Mar 1, 1994·European Journal of Biochemistry·M Pavela-VrancicH Von Döhren
Mar 1, 1996·European Journal of Biochemistry·H Kleinkauf, H Von Döhren
Jun 28, 1996·The Journal of Biological Chemistry·T SteinH R Morris
Jul 26, 1996·Biochemical Pharmacology·T StachelhausM A Marahiel
Nov 1, 1996·Chemistry & Biology·R H LambalotC T Walsh

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Citations

Jul 17, 1998·Current Opinion in Chemical Biology·H D Mootz, M A Marahiel
Jul 17, 1998·Current Opinion in Chemical Biology·C T WalshR S Flugel
Jul 29, 2009·Natural Product Reports·Alexander Koglin, Christopher T Walsh
Feb 22, 2002·European Journal of Biochemistry·Veit BergendahlMohamed A Marahiel
Dec 6, 2011·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Xiuhua LiuSujuan Xu
May 19, 2009·Journal of Bacteriology·Wan-Ju KeShih-Tung Liu
Dec 4, 2003·Journal of Bacteriology·Stephan A Sieber, Mohamed A Marahiel
Mar 10, 2006·Microbiology and Molecular Biology Reviews : MMBR·Jan Grünewald, Mohamed A Marahiel
Feb 18, 2014·Nature Chemical Biology·Nicole M Gaudelli, Craig A Townsend
Oct 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jun YinChristopher T Walsh
Oct 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Martin Hahn, Torsten Stachelhaus
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·D E EhmannC T Walsh
Dec 4, 2014·Journal of the American Chemical Society·Ti-Hsuan KuNathan C Gianneschi
Oct 15, 2009·Journal of Peptide Science : an Official Publication of the European Peptide Society·Mohamed A Marahiel
Sep 1, 2005·The FEBS Journal·Daniel B SteinMohamed A Marahiel
Jun 30, 2000·Chemistry & Biology·S Doekel, M A Marahiel
Oct 19, 2004·Annual Review of Microbiology·Robert Finking, Mohamed A Marahiel
Jul 28, 1999·Chemistry & Biology·T StachelhausM A Marahiel
Feb 18, 1999·Chemistry & Biology·D Konz, M A Marahiel
Nov 1, 1996·Chemistry & Biology·R H LambalotC T Walsh
Aug 1, 1997·Chemistry & Biology·M A Marahiel
Feb 13, 2001·Metabolic Engineering·S Doekel, M A Marahiel
Oct 12, 2000·FEMS Microbiology Letters·M C Moffitt, B A Neilan
Aug 1, 2008·Expert Opinion on Drug Discovery·Nishikant V Wase, Phillip C Wright
Aug 21, 2007·Nature Chemical Biology·Carl J BalibarChristopher T Walsh
Jun 6, 2003·Photochemistry and Photobiology·Tony Velkov, Alfons Lawen
Jan 13, 2006·Chembiochem : a European Journal of Chemical Biology·Felipe LombóJosé A Salas
Oct 10, 1997·FEBS Letters·H HusiM D Walkinshaw
Aug 7, 2012·Chembiochem : a European Journal of Chemical Biology·Viljemka Bučević-PopovićMaja Pavela-Vrančič

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