Three-dimensional structure of human cytomegalovirus protease
- 1 September 1996
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 383 (6597), 279-282
- https://doi.org/10.1038/383279a0
Abstract
Herpesviruses encode a serine protease that specifically cleaves assembly protein. This protease is critical for replication, and represents a new target for antiviral drug design. Here we report the three-dimensional structure of the protease from human cytomegalovirus (hCMV) at 2.27 angstroms resolution. The structure reveals a unique fold and new catalytic strategy for cleavage. The monomer fold of the enzyme, a seven-stranded beta-barrel encircled by a chain of helices that form the carboxy terminus of the molecule, is unrelated to those observed in classic serine proteases such as chymotrypsin and subtilisin. The serine nucleophile at position 132 is activated by two juxtaposed histidine residues at positions 63 and 157. Dimerization, which seems to be necessary for activity, is observed in the crystals. Correlations of the structure with the sequences of herpesvirus proteases suggest that dimerization may confer specificity and recognition in substrate binding.Keywords
This publication has 17 references indexed in Scilit:
- Active Human Cytomegalovirus Protease Is a DimerPublished by Elsevier BV ,1996
- Dimerization of the Human Cytomegalovirus Protease: Kinetic and Biochemical Characterization of the Catalytic HomodimerBiochemistry, 1996
- Assemblin, a herpes virus serine maturational proteinase and new molecular target for antiviralsPerspectives in Drug Discovery and Design, 1995
- Cloning and Sequence Analysis of Murine Cytomegalovirus Protease and Capsid Assembly Protein GenesBiochemical and Biophysical Research Communications, 1994
- Principles determining the structure of β-sheet barrels in proteins II. The observed structuresJournal of Molecular Biology, 1994
- Synthetic “interface” peptides alter dimeric assembly of the HIV 1 and 2 proteasesProtein Science, 1992
- A herpesvirus maturational proteinase, assemblin: identification of its gene, putative active site domain, and cleavage site.Proceedings of the National Academy of Sciences, 1991
- The high‐resolution X‐ray crystal structure of the complex formed between subtilisin Carlsberg and eglin c, an elastase inhibitor from the leech Hirudo medicinalisEuropean Journal of Biochemistry, 1987
- Analytical molecular surface calculationJournal of Applied Crystallography, 1983
- Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitorJournal of Molecular Biology, 1974