Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad.
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.
Chen
P
P
Agouron Pharmaceuticals, San Diego, California 92121, USA.
Tsuge
H
H
Almassy
R J
RJ
Gribskov
C L
CL
Katoh
S
S
Vanderpool
D L
DL
Margosiak
S A
SA
Pinko
C
C
Matthews
D A
DA
Kan
C C
CC
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
D011993:Recombinant Fusion Proteins; D010450:Endopeptidases; D012697:Serine Endopeptidases; C071910:assemblin