3NJQ
Crystal structure of Kaposi's sarcoma-associated herpesvirus protease in complex with dimer disruptor
Summary for 3NJQ
| Entry DOI | 10.2210/pdb3njq/pdb |
| Descriptor | ORF 17, ACETATE ION, 3-benzyl-4-({[6-(cyclohexylmethyl)pyridin-2-yl]carbonyl}amino)benzoic acid, ... (7 entities in total) |
| Functional Keywords | protein-dimer disruptor complex, kshv, kshv protease, herpesvirus protease, viral protein-inhibitor complex, viral protein/inhibitor |
| Biological source | Human herpesvirus 8 type M More |
| Total number of polymer chains | 2 |
| Total formula weight | 44159.12 |
| Authors | Baharuddin, A. (deposition date: 2010-06-17, release date: 2011-08-17, Last modification date: 2024-10-30) |
| Primary citation | Lee, G.M.,Shahian, T.,Baharuddin, A.,Gable, J.E.,Craik, C.S. Enzyme inhibition by allosteric capture of an inactive conformation. J.Mol.Biol., 411:999-1016, 2011 Cited by PubMed Abstract: All members of the human herpesvirus protease (HHV Pr) family are active as weakly associating dimers but inactive as monomers. A small-molecule allosteric inhibitor of Kaposi's sarcoma-associated herpesvirus protease (KSHV Pr) traps the enzyme in an inactive monomeric state where the C-terminal helices are unfolded and the hydrophobic dimer interface is exposed. NMR titration studies demonstrate that the inhibitor binds to KSHV Pr monomers with low micromolar affinity. A 2.0-Å-resolution X-ray crystal structure of a C-terminal truncated KSHV Pr-inhibitor complex locates the binding pocket at the dimer interface and displays significant conformational perturbations at the active site, 15 Å from the allosteric site. NMR and CD data suggest that the small molecule inhibits human cytomegalovirus protease via a similar mechanism. As all HHV Prs are functionally and structurally homologous, the inhibitor represents a class of compounds that may be developed into broad-spectrum therapeutics that allosterically regulate enzymatic activity by disrupting protein-protein interactions. PubMed: 21723875DOI: 10.1016/j.jmb.2011.06.032 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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