Structure of the Human Cytomegalovirus Protease Catalytic Domain Reveals a Novel Serine Protease Fold and Catalytic Triad

• Published in: Cell 1996-09, Vol.86 (5), p.835-843
• Main Authors: Chen, Ping, Tsuge, Hideaki, Almassy, Robert J., Gribskov, Cindy L., Katoh, Susumu, Vanderpool, Darin L., Margosiak, Stephen A., Pinko, Christopher, Matthews, David A., Kan, Chen-Chen
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Catalysis; Cytomegalovirus - enzymology; Endopeptidases - chemistry; human cytomegalovirus; Humans; Models, Molecular; Molecular Sequence Data; Protein Conformation; Protein Folding; Recombinant Fusion Proteins - chemistry; Sequence Alignment; Serine Endopeptidases - chemistry; X-Ray Diffraction
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80157-9

Proteolytic processing of capsid assembly protein precursors by herpesvirus proteases is essential for virion maturation. A 2.5 Å crystal structure of the human cytomegalovirus protease catalytic domain has been determined by X-ray diffraction. The structure defines a new class of serine protease with respect to global-fold topology and has a catalytic triad consisting of Ser-132, His-63, and His-157 in contrast with the Ser-His-Asp triads found in other serine proteases. However, catalytic machinery for activating the serine nucleophile and stabilizing a tetrahedral transition state is oriented similarly to that for members of the trypsin-like and subtilisin-like serine protease families. Formation of the active dimer is mediated primarily by burying a helix of one protomer into a deep cleft in the protein surface of the other.