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Kinetics, inhibition and oligomerization of Epstein‐Barr virus protease
Author(s) -
Buisson Marlyse,
Rivail Lucie,
Hernandez Jean-François,
Jamin Marc,
Martinez Jean,
Ruigrok Rob W.H.,
Burmeister Wim P.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.11.006
Subject(s) - protease , dimer , chemistry , pentapeptide repeat , enzyme , kinetics , virus , enzyme kinetics , biochemistry , epstein–barr virus , stereochemistry , non competitive inhibition , active site , peptide , microbiology and biotechnology , virology , biology , physics , organic chemistry , quantum mechanics
Epstein‐Barr virus (EBV) is an omnipresent human virus causing infectious mononucleosis and EBV associated cancers. Its protease is a possible target for antiviral therapy. We studied its dimerization and enzyme kinetics with two enzyme assays based either on the release of paranitroaniline or 7‐amino‐4‐methylcoumarin from labeled pentapeptide (Ac‐KLVQA) substrates. The protease is in a monomer–dimer equilibrium where only dimers are active. In absence of citrate the K d is 20 μM and drops to 0.2 μM in presence of 0.5 M citrate. Citrate increases additionally the activity of the catalytic sites. The inhibitory constants of different substrate derived peptides and α‐keto‐amide based inhibitors, which have at best a K i of 4 μM, have also been evaluated.