3NJQ

Crystal structure of Kaposi's sarcoma-associated herpesvirus protease in complex with dimer disruptor

3NJQ の概要

• エントリーDOI: 10.2210/pdb3njq/pdb
• 分子名称: ORF 17, ACETATE ION, 3-benzyl-4-({[6-(cyclohexylmethyl)pyridin-2-yl]carbonyl}amino)benzoic acid, ... (7 entities in total)
• 機能のキーワード: protein-dimer disruptor complex, kshv, kshv protease, herpesvirus protease, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Human herpesvirus 8 type M; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44159.12

構造登録者

Baharuddin, A. (登録日: 2010-06-17, 公開日: 2011-08-17, 最終更新日: 2024-10-30)

主引用文献

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

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: 21723875
DOI: 10.1016/j.jmb.2011.06.032

実験手法

X-RAY DIFFRACTION (2 Å)