PMID: 9420267Jan 7, 1998Paper

Mutagenesis of the NS3 protease of dengue virus type 2

Journal of Virology
R P Valle, B Falgout

Abstract

The flavivirus protease is composed of two viral proteins, NS2B and NS3. The amino-terminal portion of NS3 contains sequence and structural motifs characteristic of bacterial and cellular trypsin-like proteases. We have undertaken a mutational analysis of the region of NS3 which contains the catalytic serine, five putative substrate binding residues, and several residues that are highly conserved among flavivirus proteases and among all serine proteases. In all, 46 single-amino-acid substitutions were created in a cloned NS2B-NS3 cDNA fragment of dengue virus type 2, and the effect of each mutation on the extent of self-cleavage of the NS2B-NS3 precursor at the NS2B-NS3 junction was assayed in vivo. Twelve mutations almost completely or completely inhibited protease activity, 9 significantly reduced it, 14 decreased cleavage, and 11 yielded wild-type levels of activity. Substitution of alanine at ultraconserved residues abolished NS3 protease activity. Cleavage was also inhibited by substituting some residues that are conserved among flavivirus NS3 proteins. Two (Y150 and G153) of the five putative substrate binding residues could not be replaced by alanine, and only Y150 and N152 could be replaced by a conservative change. The...Continue Reading

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Citations

May 7, 2014·The American Journal of Tropical Medicine and Hygiene·Karen E OcwiejaAruna Dharshan De Silva
Jun 20, 2001·The Journal of General Virology·A E MatusanP J Wright
Sep 19, 2002·The Journal of General Virology·X de LamballerieE A Gould
Apr 17, 2014·Pathogens and Disease·Luwanika MleraMarshall E Bloom
Apr 9, 2016·Biochemistry Research International·R BalajeeP Gunasekaran
Dec 4, 2019·Vector Borne and Zoonotic Diseases·Monica A McArthurAlan D T Barrett
Nov 27, 2004·Journal of Virology·Pornwaratt NiyomrattanakitGerd Katzenmeier
Oct 13, 2010·Antimicrobial Agents and Chemotherapy·Chi-Chen YangAndrew Yueh
May 7, 2002·Journal of Virology·Grigori G Prikhod'koJeffrey I Cohen
Feb 29, 2020·Journal of Biomolecular Structure & Dynamics·Vivek Dhar DwivediSang Gu Kang
Aug 14, 2013·The Journal of General Virology·Jolanta KolodziejekNorbert Nowotny
Aug 18, 2017·Wiley Interdisciplinary Reviews. RNA·Carolin BrandBrian J Geiss
Nov 18, 2017·Archives of Virology·Camyla Alves LeonelJaqueline Maria Siqueira Ferreira
Aug 26, 2010·Journal of Biomedical Science·Wanisa SalaemaeGerd Katzenmeier
Mar 28, 2017·Biochemical and Biophysical Research Communications·D Aguilera-PesantesM A Méndez
Jun 11, 2002·Biochemical and Biophysical Research Communications·Natale ScaramozzinoDaniel Garin
Jan 11, 2000·Clinical Microbiology Reviews·P LeyssenJ Neyts
Sep 19, 2003·Trends in Microbiology·Christine Chevillon, Anna-Bella Failloux
Jun 22, 2021·Access Microbiology·Kim R BlasdellCadhla Firth
Oct 3, 2013·Journal of Medicinal Chemistry·Christoph NitscheChristian D Klein
Oct 1, 2014·Chemical Reviews·Christoph NitscheChristian D Klein

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