1O6E

Epstein-Barr virus protease

1O6E の概要

• エントリーDOI: 10.2210/pdb1o6e/pdb
• 分子名称: CAPSID PROTEIN P40, PHOSPHORYLISOPROPANE (3 entities in total)
• 機能のキーワード: proteinase, beta-barrel, hydrolase, serine protease, structural proteomics in europe, spine, structural genomics
• 由来する生物種: HUMAN HERPESVIRUS 4 (HUMAN HERPESVIRUS 4)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51128.13

構造登録者

Buisson, M.,Hernandez, J.,Lascoux, D.,Schoehn, G.,Forest, E.,Arlaud, G.,Seigneurin, J.,Ruigrok, R.W.H.,Burmeister, W.P. (登録日: 2002-09-13, 公開日: 2002-11-14, 最終更新日: 2024-10-23)

主引用文献

Buisson, M.,Hernandez, J.,Lascoux, D.,Schoehn, G.,Forest, E.,Arlaud, G.,Seigneurin, J.,Ruigrok, R.W.H.,Burmeister, W.P.
The Crystal Structure of the Epstein-Barr Virus Protease Shows Rearrangement of the Processed C Terminus
J.Mol.Biol., 324:89-, 2002

PubMed Abstract: Epstein-Barr virus (EBV) belongs to the gamma-herpesvirinae subfamily of the Herpesviridae. The protease domain of the assemblin protein of herpesviruses forms a monomer-dimer equilibrium in solution. The protease domain of EBV was expressed in Escherichia coli and its structure was solved by X-ray crystallography to 2.3A resolution after inhibition with diisopropyl-fluorophosphate (DFP). The overall structure confirms the conservation of the homodimer and its structure throughout the alpha, beta, and gamma-herpesvirinae. The substrate recognition could be modelled using information from the DFP binding, from a crystal contact, suggesting that the substrate forms an antiparallel beta-strand extending strand beta5, and from the comparison with the structure of a peptidomimetic inhibitor bound to cytomegalovirus protease. The long insert between beta-strands 1 and 2, which was disordered in the KSHV protease structure, was found to be ordered in the EBV protease and shows the same conformation as observed for proteases in the alpha and beta-herpesvirus families. In contrast to previous structures, the long loop located between beta-strands 5 and 6 is partially ordered, probably due to DFP inhibition and a crystal contact. It also contributes to substrate recognition. The protease shows a specific recognition of its own C terminus in a binding pocket involving residue Phe210 of the other monomer interacting across the dimer interface. This suggests conformational changes of the protease domain after its release from the assemblin precursor followed by burial of the new C terminus and a possible effect onto the monomer-dimer equilibrium. The importance of the processed C terminus was confirmed using a mutant protease carrying a C-terminal extension and a mutated release site, which shows different solution properties and a strongly reduced enzymatic activity.

PubMed: 12421561
DOI: 10.1016/S0022-2836(02)01040-9

実験手法

X-RAY DIFFRACTION (2.3 Å)