Linearization of a naturally occurring circular protein maintains structure but eliminates hemolytic activity

Biochemistry
Daniel G BarryDavid J Craik

Abstract

Cyclotides are a recently discovered family of disulfide rich proteins from plants that contain a circular protein backbone. They are exceptionally stable, as exemplified by their use in native medicine of the prototypic cyclotide kalata B1. The peptide retains uterotonic activity after the plant from which it is derived is boiled to make a medicinal tea. The circular backbone is thought to be in part responsible for the stability of the cyclotides, and to investigate its role in determining structure and biological activity, an acyclic derivative, des-(24-28)-kalata B1, was chemically synthesized and purified. This derivative has five residues removed from the 29-amino acid circular backbone of kalata B1 in a loop region corresponding to a processing site in the biosynthetic precursor protein. Two-dimensional NMR spectra of the peptide were recorded, assigned, and used to identify a series of distance, angle, and hydrogen bonding restraints. These were in turn used to determine a representative family of solution structures. Of particular interest was a determination of the structural similarities and differences between des-(24-28)-kalata B1 and native kalata B1. Although the overall three-dimensional fold remains very simila...Continue Reading

References

Nov 1, 1992·Journal of Biomolecular NMR·M PiottoV Sklenár
Jul 1, 1991·Journal of Biomolecular NMR·C EcclesK Wüthrich
Dec 16, 1983·Biochemical and Biophysical Research Communications·M RanceK Wüthrich
Feb 1, 1996·Protein Science : a Publication of the Protein Society·E G Hutchinson, J M Thornton
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Nov 21, 1997·Journal of Molecular Biology·P GüntertK Wüthrich
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·J P TamK W Chiu
Oct 13, 1999·FEBS Letters·H Iwai, A Plückthun
Aug 6, 2000·Acta Crystallographica. Section B, Structural Science·V A BlatovV N Serezhkin
Aug 11, 2000·Toxicon : Official Journal of the International Society on Toxinology·D J CraikC Waine
Apr 9, 2001·The Journal of Biological Chemistry·M E Felizmenio-QuimioD J Craik
Sep 6, 2001·Proceedings of the National Academy of Sciences of the United States of America·C JenningsM Anderson
Dec 14, 2001·The Journal of Biological Chemistry·Neal K WilliamsNicholas E Dixon
Mar 13, 2002·Archives of Biochemistry and Biophysics·Lars SkjeldalBrian F Volkman
Mar 15, 2002·Trends in Biochemical Sciences·Manuela Trabi, David J Craik
May 2, 2002·Journal of the American Chemical Society·Songpon Deechongkit, Jeffery W Kelly
Dec 17, 2002·The Journal of Biological Chemistry·K Johan RosengrenDavid J Craik

❮ Previous
Next ❯

Citations

Nov 27, 2009·Biotechnology Letters·Qing-long LiangHong-xuan He
Jul 1, 2009·Physiology and Molecular Biology of Plants : an International Journal of Functional Plant Biology·B K SalunkeV L Maheshwari
Mar 25, 2009·The Journal of Organic Chemistry·Reshma JagasiaM G Finn
Jan 26, 2012·Journal of Natural Products·Carsten GründemannChristian W Gruber
Mar 21, 2007·Molecular BioSystems·David J Craik, Norelle L Daly
Aug 1, 2009·Natural Product Reports·John A McIntoshEric W Schmidt
Jan 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Barbara L BarbetaMarilyn A Anderson
Jun 6, 2009·The Journal of Biological Chemistry·Yen-Hua HuangDavid J Craik
Oct 8, 2011·The Journal of Biological Chemistry·Giang Kien Truc NguyenJames P Tam
Jun 16, 2012·The Journal of Biological Chemistry·Aaron G PothDavid J Craik
Oct 27, 2007·Antioxidants & Redox Signaling·Masa CemazarDavid J Craik
Mar 10, 2010·Antimicrobial Agents and Chemotherapy·Michelle L ColgraveAndrew C Kotze
Dec 17, 2008·BMC Structural Biology·Annie HeitzLaurent Chiche
Dec 13, 2005·Biological Chemistry·Olga AvrutinaHarald Kolmar
Sep 14, 2010·Organic & Biomolecular Chemistry·Laura Cascales, David J Craik
Oct 2, 2009·Cellular and Molecular Life Sciences : CMLS·David J CraikNorelle L Daly
Oct 25, 2011·Expert Opinion on Therapeutic Patents·Amanda B SmithDavid J Craik
Apr 4, 2012·Expert Opinion on Drug Discovery·David J CraikMasa Cemazar
Nov 24, 2004·FEBS Letters·Shane M SimonsenDavid J Craik
Mar 31, 2015·BioMed Research International·Jaquelina Julia Guzmán-RodríguezJoel E López-Meza
Mar 12, 2010·Toxicon : Official Journal of the International Society on Toxinology·David J Craik
May 9, 2009·Trends in Plant Science·David J Craik
Jul 5, 2008·Trends in Biochemical Sciences·Ivana Saska, David J Craik
Nov 17, 2007·Biopolymers·David C IrelandDavid J Craik
May 9, 2008·Biopolymers·Joshua S Mylne, David J Craik
May 31, 2007·Chembiochem : a European Journal of Chemical Biology·Manuel Rey R PlanDavid J Craik
Oct 31, 2008·Chemistry & Biodiversity·Lorents GranLars Skjeldal
Dec 19, 2007·The Plant Journal : for Cell and Molecular Biology·Amanda D GillonMarilyn A Anderson
Sep 20, 2011·Chembiochem : a European Journal of Chemical Biology·Lillian SandoDavid J Craik
Jun 22, 2010·Biopolymers·Joshua S MylneDavid J Craik
Aug 1, 2014·Angewandte Chemie·Anne C Conibear, David J Craik
Jul 6, 2014·European Journal of Medicinal Chemistry·Charlotte D'SouzaDavid J Craik
Apr 23, 2015·Journal of Chemical Information and Modeling·Andreas TruszkowskiMatthias Epple
Dec 7, 2010·Biochimie·Manuel Montalbán-LópezMercedes Maqueda
Apr 28, 2012·Biochimica Et Biophysica Acta·Kristopher HallMarie-Isabel Aguilar
Jan 21, 2012·ACS Chemical Biology·Sónia Troeira Henriques, David J Craik

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.