title: Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad.
abstract: Proteolytic processing of capsid assembly protein precursors by herpesvirus proteases is essential for virion maturation. A 2.5 A 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.
authors.affiliation: Agouron Pharmaceuticals, San Diego, California 92121, USA.
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Tsuge
authors.forename: R J
authors.initials: RJ
authors.lastname: Almassy
authors.forename: C L
authors.initials: CL
authors.lastname: Gribskov
authors.forename: S
authors.initials: S
authors.lastname: Katoh
authors.forename: D L
authors.initials: DL
authors.lastname: Vanderpool
authors.forename: S A
authors.initials: SA
authors.lastname: Margosiak
authors.forename: C
authors.initials: C
authors.lastname: Pinko
authors.forename: D A
authors.initials: DA
authors.lastname: Matthews
authors.forename: C C
authors.initials: CC
authors.lastname: Kan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D003587:Cytomegalovirus / Q000201:enzymology*; D010450:Endopeptidases / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D011993:Recombinant Fusion Proteins; D010450:Endopeptidases; D012697:Serine Endopeptidases; C071910:assemblin