 |
PDBsum entry 1lvo
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-Helical domain.
|
|
|
Authors
|
|
K.Anand,
G.J.Palm,
J.R.Mesters,
S.G.Siddell,
J.Ziebuhr,
R.Hilgenfeld.
|
|
|
Ref.
|
|
EMBO J, 2002,
21,
3213-3224.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The key enzyme in coronavirus polyprotein processing is the viral main
proteinase, M(pro), a protein with extremely low sequence similarity to other
viral and cellular proteinases. Here, the crystal structure of the 33.1 kDa
transmissible gastroenteritis (corona)virus M(pro) is reported. The structure
was refined to 1.96 A resolution and revealed three dimers in the asymmetric
unit. The mutual arrangement of the protomers in each of the dimers suggests
that M(pro) self-processing occurs in trans. The active site, comprised of
Cys144 and His41, is part of a chymotrypsin-like fold that is connected by a 16
residue loop to an extra domain featuring a novel alpha-helical fold. Molecular
modelling and mutagenesis data implicate the loop in substrate binding and
elucidate S1 and S2 subsites suitable to accommodate the side chains of the P1
glutamine and P2 leucine residues of M(pro) substrates. Interactions involving
the N-terminus and the alpha-helical domain stabilize the loop in the
orientation required for trans-cleavage activity. The study illustrates that RNA
viruses have evolved unprecedented variations of the classical chymotrypsin fold.
|
|
|
|
|
|
|
|
Figure 7.
Figure 7 Stereo diagram of a P5−P1 substrate
(Asn−Ser−Thr−Leu−Gln, red; corresponding to the TGEV
M^pro N-terminal autoprocessing site) modelled into the active
site cleft of the TGEV M^pro. Hydrogen bonds are depicted by
dotted lines.
|
|
Figure 8.
Figure 8 Intra- and intermolecular contacts of the TGEV M^pro
N-terminus. (A) MOLSCRIPT stereo representation of a TGEV M^pro
dimer. Molecule A is coloured from blue at the N-terminus, via
green (domain II), to red (C-terminus), while molecule B is
shown in grey. The catalytic Cys144 and His41 residues are
labelled in both monomers. (B) Detailed view of the interactions
made by the N-terminal segment (blue) and domains II/III of
monomer A as well as domains II/III of monomer B. Residues
critically involved in these interactions are designated by the
single-letter code and shown in ball-and-stick representation
(see text for details). The N- and C-termini of molecule A are
indicated.
|
|
|
|
|
|
The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2002,
21,
3213-3224)
copyright 2002.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Virus-Encoded proteinases and proteolytic processing in the nidovirales.
|
|
|
Authors
|
|
J.Ziebuhr,
E.J.Snijder,
A.E.Gorbalenya.
|
|
|
Ref.
|
|
J Gen Virol, 2000,
81,
853-879.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
