title: Crystal structure of varicella-zoster virus protease.
abstract: Varicella-zoster virus (VZV), an alpha-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-A 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 beta 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 alpha-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.
authors.affiliation: Department of Macromolecular Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
authors.forename: X
authors.initials: X
authors.lastname: Qiu
authors.forename: C A
authors.initials: CA
authors.lastname: Janson
authors.forename: J S
authors.initials: JS
authors.lastname: Culp
authors.forename: S B
authors.initials: SB
authors.lastname: Richardson
authors.forename: C
authors.initials: C
authors.lastname: Debouck
authors.forename: W W
authors.initials: WW
authors.lastname: Smith
authors.forename: S S
authors.initials: SS
authors.lastname: Abdel-Meguid
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D018360:Crystallography, X-Ray; D014645:Herpesvirus 3, Human / Q000201:enzymology*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D012697:Serine Endopeptidases; C105484:varicella-zoster virus protease