PMID: 11916396Mar 28, 2002Paper

Engineering an obligate domain-swapped dimer of cyanovirin-N with enhanced anti-HIV activity

Journal of the American Chemical Society
Brendan S KelleyC A Bewley

Abstract

The anti-HIV cyanobacterial protein cyanovirin-N can undergo domain swapping to form an intertwined dimer. The dimeric form is stable at low pH and millimolar concentrations. By deleting an amino acid from the hinge linker about which domain swapping occurs, we have constructed an obligate domain-swapped dimer of cyanovirin-N that represents a new tetravalent carbohydrate binding protein that is stable over a large range of pH values. This obligate dimer displays enhanced anti-HIV activity relative to the wild-type cyanovirin-N monomer with an observed 3.5-fold decrease in IC(50) (9nM for the dimer vs 32 nM for the monomer) for inhibition of HIV-1 envelope-mediated cell fusion and, when expressed in Escherichia coli, can be rapidly obtained in >98% purity in a single chromatographic step.

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Citations

Oct 22, 2003·Current Opinion in Structural Biology·Heide KogelbergJesús Jiménez-Barbero
Feb 3, 2012·Journal of the American Chemical Society·Lin LiuAngela M Gronenborn
Oct 13, 2012·Journal of the American Chemical Society·Yukiji K Fujimoto, David F Green
Oct 2, 2002·Nature Genetics·Abdallah S DaarPeter A Singer
May 17, 2011·Nature Structural & Molecular Biology·Jeremie VendomeBarry Honig
Jul 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jennifer R KeeffeStephen L Mayo
Aug 25, 2004·Proteins·Yves-Henri Sanejouand
Jan 20, 2006·Molecular Microbiology·Jan-Christoph KehrElke Dittmann
Apr 26, 2008·Protein Science : a Publication of the Protein Society·Raimund FrommeGiovanna Ghirlanda
Jun 11, 2002·Biochemical and Biophysical Research Communications·Istvan BotosAlexander Wlodawer
Jul 4, 2012·Biotechnology Advances·Hester C T Lotter-StarkRachel K Chikwamba
Jan 24, 2009·Current Opinion in Structural Biology·Angela M Gronenborn
Oct 2, 2004·Structure·Laura G BarrientosAngela M Gronenborn
Dec 2, 2004·Progress in Biophysics and Molecular Biology·Istvan Botos, Alexander Wlodawer
May 1, 2017·The FEBS Journal·Alonso I CarvajalJorge Babul
Nov 3, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuichiro Sato
Oct 3, 2006·Protein Engineering, Design & Selection : PEDS·Laura G BarrientosAngela M Gronenborn
Jun 21, 2013·Biopolymers·Carole A Bewley, Syed Shahzad-Ul-Hussan
Aug 5, 2018·Nature Structural & Molecular Biology·Laura McPartlandMichael R Sawaya
Feb 15, 2014·Biochemistry·Sai Kumar RamaduguClaudio J Margulis

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