Journal
BIOCHEMISTRY
Volume 39, Issue 42, Pages 12796-12803Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi001019h
Keywords
-
Categories
Funding
- NIGMS NIH HHS [GM08204, GM56531] Funding Source: Medline
Ask authors/readers for more resources
The structure of Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr), at 2.2 Angstrom resolution, reveals the active-site geometry and defines multiple possible target sites fur drug design against a human cancer-producing virus. The catalytic triad of KSWV Pr, (Ser114, His46, and His157) and Transition-state stabilization site are arranged as in other structurally characterized herpesviral proteases. The distal histidine-histidine hydrogen bond is solvent accessible, unlike the situation in other classes of serine proteases. As in all herpesviral proteases, the enzyme is active only as a weakly associated dimer (K-d approximate to 2 muM), and inactive as a monomer. Therefore, both the active site and dimer interface are potential targets for antiviral drug design. The dimer interface in KSHV Pr is compared with the interface of other herpesviral proteases. Two conserved arginines (Arg209), one from each monomer, are buried within the same region of the dimer interface, We propose that this conserved arginine may provide a destabilizing element contributing to the tuned micromolar dissociation of herpesviral protease dimers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available