Open AccessCrystal structure of varicella-zoster virus protease
Author(s) -
Xiayang Qiu,
Cheryl A. Janson,
Jeffrey S. Culp,
Susan B. Richardson,
Christine Debouck,
Ward W. Smith,
Sherin S. Abdel-Meguid
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.7.2874
Subject(s) - proteases , varicella zoster virus , virus , virology , protease , serine protease , ns2 3 protease , biology , catalytic triad , masp1 , serine , enzyme , biochemistry , viral replication
Varicella-zoster virus (VZV), an α-herpes virus, is the causative agent of chickenpox, shingles, and postherpetic neuralgia. The three-dimensional crystal structure of the serine protease from VZV has been determined at 3.0-Å resolution. The VZV protease is essential for the life cycle of the virus and is a potential target for therapeutic intervention. The structure reveals an overall fold that is similar to that recently reported for the serine protease from cytomegalovirus (CMV), a herpes virus of the β subfamily. The VZV protease structure provides further evidence to support the finding that herpes virus proteases have a fold and active site distinct from other serine proteases. The VZV protease catalytic triad consists of a serine and two histidines. The distal histidine is proposed to properly orient the proximal histidine. The identification of an α-helical segment in the VZV protease that was mostly disordered in the CMV protease provides a better definition of the postulated active site cavity and reveals an elastase-like S′ region. Structural differences between the VZV and CMV proteases also suggest potential differences in their oligomerization states.