Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.
Journal, issue, pages	PLoS Pathog, Vol. 11, Issue 7, Page e1005045, Year 2015
Publish date	Jul 10, 2015
Authors	Martin Zühlsdorf / Sebastiaan Werten / Barbara G Klupp / Gottfried J Palm / Thomas C Mettenleiter / Winfried Hinrichs /
PubMed Abstract	Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such ...Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an active dimeric form of the enzyme, which is believed to play a key regulatory role in the orchestration of proteolysis and capsid assembly. Currently available crystal structures of herpesvirus proteases correspond either to the dimeric state or to complexes with peptide mimetics that alter the dimerization interface. In contrast, the structure of the native monomeric state has remained elusive. Here, we present the three-dimensional structures of native monomeric, active dimeric, and diisopropyl fluorophosphate-inhibited dimeric protease derived from pseudorabies virus, an alphaherpesvirus of swine. These structures, solved by X-ray crystallography to respective resolutions of 2.05, 2.10 and 2.03 Å, allow a direct comparison of the main conformational states of the protease. In the dimeric form, a functional oxyanion hole is formed by a loop of 10 amino-acid residues encompassing two consecutive arginine residues (Arg136 and Arg137); both are strictly conserved throughout the herpesviruses. In the monomeric form, the top of the loop is shifted by approximately 11 Å, resulting in a complete disruption of the oxyanion hole and loss of activity. The dimerization-induced allosteric changes described here form the physical basis for the concentration-dependent activation of the protease, which is essential for proper virus replication. Small-angle X-ray scattering experiments confirmed a concentration-dependent equilibrium of monomeric and dimeric protease in solution.
External links	PLoS Pathog / PubMed:26161660 / PubMed Central
Methods	SAS (X-ray synchrotron) / X-ray diffraction
Resolution	2.03 - 2.53 Å
Structure data	SASDA58: UL26N of pseudorabies virus (VP24, UL26N) Method: SAXS/SANS PDB-4cx8: Monomeric pseudorabies virus protease pUL26N at 2.5 A resolution Method: X-RAY DIFFRACTION / Resolution: 2.53 Å PDB-4v07: Dimeric pseudorabies virus protease pUL26N at 2.1 A resolution Method: X-RAY DIFFRACTION / Resolution: 2.1 Å PDB-4v08: Inhibited dimeric pseudorabies virus protease pUL26N at 2 A resolution Method: X-RAY DIFFRACTION / Resolution: 2.03 Å PDB-4v0t: Monomeric pseudorabies virus protease pUL26N at 2.1 A resolution Method: X-RAY DIFFRACTION / Resolution: 2.05 Å
Chemicals	ChemComp-HOH: WATER ChemComp-CL: Unknown entry ChemComp-MG: Unknown entry ChemComp-DFP: DIISOPROPYL PHOSPHONATE
Source	suid herpesvirus 1
Keywords	VIRAL PROTEIN / ASSEMBLIN / UL26 / PRV / UL26P / SERINE PROTEASE / HERPES / HERPES VIRUS / PROTEASE / SUID / HYDROLASE