CRYSTAL-STRUCTURE OF VARICELLA-ZOSTER VIRUS PROTEASE

Varicella-zoster virus (VZV), an alpha-herpes virus, is the causative agent of chickenpox, shingles, and postherpetic neuralgia, The three-d imensional crystal structure of the serine protease from VZV has been determined at 3.0-Angstrom resolution, The VZV protease is essential f or the life cycle of the virus and is a potential target for therapeut ic intervention, The structure reveals an overall fold that Is similar to that recently reported for the serine protease from cytomegaloviru s (CMV), a herpes virus of the beta subfamily, The VZV protease struct ure provides further evidence to support the finding that herpes virus proteases have a fold and active site distinct from other serine prot eases, The VZV protease catalytic triad consists of a serine and two h istidines, The distal histidine is proposed to properly orient the pro ximal histidine, The identification of an cu-helical segment in the VZ V protease that was mostly disordered in the CMS: protease provides a better definition of the postulated active site cavity and reveals an elastase-like S' region, Structural differences between the VZV and CM V proteases also suggest potential differences in their oligomerizatio n states.