2PBK

Crystal structure of KSHV protease in complex with hexapeptide phosphonate inhibitor

2PBK の概要

• エントリーDOI: 10.2210/pdb2pbk/pdb
• 関連するPDBエントリー: 1FL1
• 関連するBIRD辞書のPRD_ID: PRD_000347
• 分子名称: KSHV protease, hexapeptide phosphonate inhibitor, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: kshv, kshv protease, herpesvirus protease, viral protease, viral protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human herpesvirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 51736.07

構造登録者

Lazic, A.,Goetz, D.H. (登録日: 2007-03-28, 公開日: 2007-12-25, 最終更新日: 2024-10-16)

主引用文献

Lazic, A.,Goetz, D.H.,Nomura, A.M.,Marnett, A.B.,Craik, C.S.
Substrate modulation of enzyme activity in the herpesvirus protease family.
J.Mol.Biol., 373:913-923, 2007

PubMed Abstract: The herpesvirus proteases are an example in which allosteric regulation of an enzyme activity is achieved through the formation of quaternary structure. Here, we report a 1.7 A resolution structure of Kaposi's sarcoma-associated herpesvirus protease in complex with a hexapeptide transition state analogue that stabilizes the dimeric state of the enzyme. Extended substrate binding sites are induced upon peptide binding. In particular, 104 A2 of surface are buried in the newly formed S4 pocket when tyrosine binds at this site. The peptide inhibitor also induces a rearrangement of residues that stabilizes the oxyanion hole and the dimer interface. Concomitant with the structural changes, an increase in catalytic efficiency of the enzyme results upon extended substrate binding. A nearly 20-fold increase in kcat/KM results upon extending the peptide substrate from a tetrapeptide to a hexapeptide exclusively due to a KM effect. This suggests that the mechanism by which herpesvirus proteases achieve their high specificity is by using extended substrates to modulate both the structure and activity of the enzyme.

PubMed: 17870089
DOI: 10.1016/j.jmb.2007.07.073

実験手法

X-RAY DIFFRACTION (1.73 Å)