1o6e
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Epstein-Barr virus (EBV) belongs to the gamma-herpesvirinae subfamily of | + | 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. |
==About this Structure== | ==About this Structure== | ||
| Line 16: | Line 16: | ||
[[Category: Arlaud, G.]] | [[Category: Arlaud, G.]] | ||
[[Category: Buisson, M.]] | [[Category: Buisson, M.]] | ||
| - | [[Category: Burmeister, W | + | [[Category: Burmeister, W P.]] |
[[Category: Forest, E.]] | [[Category: Forest, E.]] | ||
[[Category: Hernandez, J.]] | [[Category: Hernandez, J.]] | ||
[[Category: Lascoux, D.]] | [[Category: Lascoux, D.]] | ||
| - | [[Category: Ruigrok, R | + | [[Category: Ruigrok, R W.H.]] |
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: Schoehn, G.]] | [[Category: Schoehn, G.]] | ||
[[Category: Seigneurin, J.]] | [[Category: Seigneurin, J.]] | ||
| Line 37: | Line 37: | ||
[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:13:56 2008'' |
Revision as of 12:13, 21 February 2008
|
EPSTEIN-BARR VIRUS PROTEASE
Overview
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.
About this Structure
1O6E is a Single protein structure of sequence from Human herpesvirus 4 with as ligand. Active as Assemblin, with EC number 3.4.21.97 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
The crystal structure of the Epstein-Barr virus protease shows rearrangement of the processed C terminus., Buisson M, Hernandez JF, Lascoux D, Schoehn G, Forest E, Arlaud G, Seigneurin JM, Ruigrok RW, Burmeister WP, J Mol Biol. 2002 Nov 15;324(1):89-103. PMID:12421561
Page seeded by OCA on Thu Feb 21 14:13:56 2008
Categories: Assemblin | Human herpesvirus 4 | Single protein | Arlaud, G. | Buisson, M. | Burmeister, W P. | Forest, E. | Hernandez, J. | Lascoux, D. | Ruigrok, R W.H. | SPINE, Structural Proteomics in Europe. | Schoehn, G. | Seigneurin, J. | MIP | Beta-barrel | Coat protein | Domain | Hydrolase | Protease | Proteinase | Serine protease | Spine | Structural genomics | Structural proteomics in europe
