 |
PDBsum entry 4wur
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structural and mutational analysis of the interaction between the middle-East respiratory syndrome coronavirus (mers-Cov) papain-Like protease and human ubiquitin.
|
|
|
Authors
|
|
J.Lei,
R.Hilgenfeld.
|
|
|
Ref.
|
|
Virol Sin, 2016,
31,
288-299.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
|
|
|
|
Abstract
|
|
|
The papain-like protease (PL(pro)) of Middle-East respiratory syndrome
coronavirus (MERS-CoV) has proteolytic, deubiquitinating, and deISGylating
activities. The latter two are involved in the suppression of the antiviral
innate immune response of the host cell. To contribute to an understanding of
this process, we present here the X-ray crystal structure of a complex between
MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage
between the two proteins. Five regions of the PL(pro) bind to two areas of the
Ub. The C-terminal five residues of Ub, RLRGG, are similar to the P5-P1 residues
of the polyprotein substrates of the PL(pro) and are responsible for the major
part of the interaction between the two macromolecules. Through sitedirected
mutagenesis, we demonstrate that conserved Asp165 and non-conserved Asp164 are
important for the catalytic activities of MERS-CoV PL(pro). The enzyme appears
not to be optimized for catalytic efficiency; thus, replacement of Phe269 by Tyr
leads to increased peptidolytic and deubiquitinating activities. Ubiquitin
binding by MERS-CoV PL(pro) involves remarkable differences compared to the
corresponding complex with SARS-CoV PL(pro). The structure and the mutational
study help understand common and unique features of the deubiquitinating
activity of MERS-CoV PL(pro).
|
|
|
|
|
|
|
