Lysine-scanning mutagenesis reveals an amendable face of the cyclotide kalata B1 for the optimization of nematocidal activity.

The Journal of Biological Chemistry
Yen-Hua HuangDavid J Craik

Abstract

Cyclotides are a family of macrocyclic peptides that combine the unique features of a head-to-tail cyclic backbone and a cystine knot motif, the combination of which imparts them with extraordinary stability. The prototypic cyclotide kalata B1 is toxic against two economically important gastrointestinal nematode parasites of sheep, Haemonchus contortus and Trichostrongylus colubriformis. A lysine scan was conducted to examine the effect of the incorporation of positive charges into the kalata B1 cyclotide framework. Each of the non-cysteine residues in this 29-amino acid peptide was successively substituted with lysine, and the nematocidal and hemolytic activities of the suite of mutants were determined. Substitution of 11 residues within kalata B1 decreased the nematocidal activity dramatically. On the other hand, six other residues that are clustered on the surface of kalata B1 were tolerant to Lys substitution, and indeed the introduction of positively charged residues into this region increased nematocidal activity. This activity was increased further in double and triple lysine mutants, with a maximal increase (relative to the native kalata B1) of 13-fold obtained with a triple lysine mutant (mutated at positions Thr-20, A...Continue Reading

References

Sep 1, 1992·International Journal of Peptide and Protein Research·M SchnölzerS B Kent
Nov 4, 1994·Science·P E DawsonS B Kent
Apr 21, 1998·Journal of Natural Products·P ClaesonL Bohlin
Jul 31, 1998·Protein Science : a Publication of the Protein Society·J P Tam, Y A Lu
Mar 17, 1999·Journal of Natural Products·U GöranssonP Claeson
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·J P TamK W Chiu
May 18, 2000·The Journal of Organic Chemistry·Y F HallockM R Boyd
Apr 9, 2001·The Journal of Biological Chemistry·M E Felizmenio-QuimioD J Craik
Aug 29, 2001·Phytochemistry·A M BroussalisP Claeson
Sep 6, 2001·Proceedings of the National Academy of Sciences of the United States of America·C JenningsM Anderson
Oct 16, 2001·Toxicon : Official Journal of the International Society on Toxinology·D J Craik
Dec 4, 2001·International Journal for Parasitology·A C Kotze, S J McClure
Dec 17, 2002·The Journal of Biological Chemistry·Norelle L DalyDavid J Craik
Dec 17, 2002·The Journal of Biological Chemistry·K Johan RosengrenDavid J Craik
Jun 3, 2004·Experimental Parasitology·J O'Grady, A C Kotze
Aug 31, 2004·Journal of Natural Products·Ulf GöranssonLars Bohlin
Sep 15, 2004·Trends in Parasitology·Adrian J WolstenholmeNicholas C Sangster
Sep 15, 2004·Trends in Parasitology·Ray M Kaplan
Nov 17, 2004·Current Protein & Peptide Science·David J CraikManuela Trabi
Jan 4, 2006·Cellular and Molecular Life Sciences : CMLS·A HerrmannU Göransson
Jan 31, 2006·Journal of Natural Products·Bin ChenDavid J Craik
Nov 23, 2006·Trends in Parasitology·Brown Besier
Jan 17, 2007·Toxicon : Official Journal of the International Society on Toxinology·Christian W GruberDavid J Craik
May 22, 2007·Biochemical Society Transactions·S CurryR J Leatherbarrow
Nov 17, 2007·Biopolymers·David C IrelandDavid J Craik
Dec 18, 2007·Journal of Natural Products·Conan K L WangDavid J Craik
Jan 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Barbara L BarbetaMarilyn A Anderson
Feb 9, 2008·The Journal of Biological Chemistry·Shane M SimonsenDavid J Craik
Apr 4, 2008·Organic & Biomolecular Chemistry·Panumart ThongyooEdward W Tate
Jul 12, 2008·Chembiochem : a European Journal of Chemical Biology·Michelle L ColgraveDavid J Craik
Dec 9, 2008·Acta Tropica·Michelle L ColgraveDavid J Craik
May 23, 2009·Organic & Biomolecular Chemistry·Manuela TrabiDavid J Craik
Jun 6, 2009·The Journal of Biological Chemistry·Yen-Hua HuangDavid J Craik

❮ Previous
Next ❯

Citations

Feb 4, 2011·European Biophysics Journal : EBJ·Norelle L DalyDavid J Craik
Aug 28, 2013·Chemical Reviews·Robert O J Weinzierl
Jul 16, 2013·Journal of the American Chemical Society·Yanbin JiJulio A Camarero
Nov 16, 2012·Journal of Medicinal Chemistry·Teshome L AboyeJulio A Camarero
Apr 30, 2011·The Journal of Organic Chemistry·David J Craik, Anne C Conibear
Jan 26, 2012·Journal of Natural Products·Carsten GründemannChristian W Gruber
May 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Aaron G PothDavid J Craik
Aug 30, 2011·The Journal of Biological Chemistry·Laura CascalesDavid J Craik
Aug 3, 2012·The Journal of Biological Chemistry·Sónia Troeira HenriquesDavid J Craik
Jun 16, 2012·The Journal of Biological Chemistry·Ulf GöranssonK Johan Rosengren
Mar 10, 2010·Antimicrobial Agents and Chemotherapy·Michelle L ColgraveAndrew C Kotze
Feb 23, 2013·The Journal of Biological Chemistry·Anne C ConibearDavid J Craik
Mar 16, 2011·FEBS Letters·Octavio Luiz Franco
Jan 29, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teshome AboyeJulio A Camarero
Apr 4, 2012·Expert Opinion on Drug Discovery·David J CraikMasa Cemazar
Aug 19, 2015·Chemistry & Biology·Sónia Troeira HenriquesDavid J Craik
Apr 1, 2012·Drug Discovery Today. Technologies
Mar 12, 2010·Toxicon : Official Journal of the International Society on Toxinology·David J Craik
Mar 28, 2012·Biochemical and Biophysical Research Communications·Marta M B RibeiroMiguel A R B Castanho
Sep 1, 2015·ACS Chemical Biology·Anjaneya S RavipatiDavid J Craik
Dec 5, 2014·PloS One·Wanapinun NawaeMarasri Ruengjitchatchawalya
Jan 14, 2017·Biochemistry·Sónia Troeira Henriques, David J Craik
Mar 2, 2017·Current Opinion in Chemical Biology·David J Craik, Junqiao Du
Feb 5, 2014·Scientific Reports·Wanapinun NawaeMarasri Ruengjitchatchawalya
May 26, 2017·Chembiochem : a European Journal of Chemical Biology·Andrew Gould, Julio A Camarero
Jun 14, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Charles G CranfieldBruce Cornell
Jul 26, 2017·ACS Chemical Biology·Sónia Troeira HenriquesDavid J Craik
Aug 8, 2014·Chembiochem : a European Journal of Chemical Biology·Sónia Troeira HenriquesDavid J Craik
Nov 6, 2018·ChemMedChem·Shimaa A H Abdel MonaimFernando Albericio
Jan 16, 2014·The Journal of Biological Chemistry·Xinying JiaDavid J Craik
Sep 17, 2013·Chembiochem : a European Journal of Chemical Biology·Inês M TorcatoSónia Troeira Henriques
May 18, 2020·The Journal of Biological Chemistry·Qingdan DuDavid J Craik
Apr 5, 2012·Toxins·David J Craik
Aug 16, 2018·Cellular and Molecular Life Sciences : CMLS·Bruno MadioEivind A B Undheim
Jan 13, 2019·The Biochemical Journal·Dipankar ChaudhuriJulio A Camarero
Jun 6, 2013·Journal of Peptide Science : an Official Publication of the European Peptide Society·David J Craik
Aug 29, 2019·International Journal of Molecular Sciences·Felicitas VernenSónia Troeira Henriques
Sep 14, 2018·International Journal of Molecular Sciences·Sara La MannaDaniela Marasco

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.