A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease

• Published in: Nature (London) 1996-09, Vol.383 (6597), p.272-275
• Main Authors: Tong, Liang, Qian, Chungeng, Massariol, Marie-Josée, Bonneau, Pierre R., Cordingley, Michael G., Lagacé, Lisette
• Format: Article
• Language: English
• Subjects: Amino acids; Crystallography, X-Ray; Cytomegalovirus - chemistry; Cytomegalovirus - enzymology; Endopeptidases - chemistry; Escherichia coli; Herpes viruses; herpesvirus; human cytomegalovirus; Humanities and Social Sciences; Humans; letter; Models, Molecular; Molecular biology; multidisciplinary; Peptides; Protein Conformation; Protein Folding; Protein Structure, Secondary; Recombinant Proteins - chemistry; Science; Science (multidisciplinary); Serine - chemistry; Serine Endopeptidases
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/383272a0

HUMAN cytomegalovirus (hCMV), a herpesvirus, infects up to 70% of the general population in the United States and can cause morbidity and mortality in immunosuppressed individuals (organ-transplant recipients and AIDS patients) and congenitally infected newborns 1 . hCMV protease is essential for the production of mature infectious virions, as it performs proteolytic processing near the carboxy terminus (M-site) of the viral assembly protein precursor (for a review, see ref. 2). hCMV protease is a serine protease 2 , although it has little homology to other clans of serine proteases 2,3 Here we report the crystal structure of hCMV protease at 2.0Å resolution, and show that it possesses a new polypeptide backbone fold. Ser 132 and His 63 are found in close proximity in the active site, confirming earlier biochemical and mutagenesis studies 2 . The structure suggests that the third member of the triad is probably His 157. A dimer of the protease with an extensive interface is found in the crystal structure. This structure information will help in the design and optimization of inhibitors against herpesvirus proteases.