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PDBsum entry 2j7q
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References listed in PDB file
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Key reference
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Title
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Structure of a herpesvirus-Encoded cysteine protease reveals a unique class of deubiquitinating enzymes.
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Authors
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C.Schlieker,
W.A.Weihofen,
E.Frijns,
L.M.Kattenhorn,
R.Gaudet,
H.L.Ploegh.
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Ref.
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Mol Cell, 2007,
25,
677-687.
[DOI no: ]
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PubMed id
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Abstract
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All members of the herpesviridae contain within their large tegument protein a
cysteine protease module that displays deubiquitinating activity. We report the
crystal structure of the cysteine protease domain of murine cytomegalovirus M48
(M48(USP)) in a complex with a ubiquitin (Ub)-based suicide substrate. M48(USP)
adopts a papain-like fold, with the active-site cysteine forming a thioether
linkage to the suicide substrate. The Ub core participates in an extensive
hydrophobic interaction with an exposed beta hairpin loop of M48(USP). This Ub
binding mode contributes to Ub specificity and is distinct from that observed in
other deubiquitinating enzymes. Both the arrangement of active-site residues and
the architecture of the interface with Ub lead us to classify this domain as the
founding member of a previously unknown class of deubiquitinating enzymes.
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Figure 2.
Figure 2. Fold and Structure of M48^USP-UbVME
(A) Ribbon
representation of the M48^USP structure (gray with the β
hairpin in orange) in complex with UbVME (green). The secondary
structure elements are labeled, and the side chains of catalytic
triad residues are shown in yellow.
(B) Electrostatic
surface potential representation of M48^USP with bound Ub shown
in a ribbon representation (top). Below, Ub, in an electrostatic
surface potential representation, was rotated 180° to show
the charge distribution on the face forming the interface. Note
the charge complementarity between the M48^USP acidic cleft and
the positively charged Ub C terminus.
(C) The final 2F[o]
− F[c] electron density map contoured at 1.3 σ indicates a
covalent bond between the catalytic C23 and the Cβ atom of the
former vinylmethylester moiety at the Ub C terminus.
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Figure 3.
Figure 3. Interactions between UbVME and M48^USP
(A)
Stereo view of the extended C terminus and attached VME moiety
of Ub in the M48^USP active-site cleft. M48^USP and UbVME are in
gray and green, respectively. Nitrogen atoms are shown in blue,
and oxygen atoms in red. Dashed lines indicate hydrogen bonds.
Note that the Ub C terminus features an extended β conformation
and is extensively coordinated by several hydrogen bonds to
M48^USP residues. V140 and Y76 of M48^USP are in van der Waals
contact and form a canopy over the active site.
(B) Stereo
view of the interactions between the Ub core (green) and M48^USP
(gray) or its β hairpin (orange). The gray transparent M48^USP
surface highlights the shape complementarity of the interface,
which is mainly lined by hydrophobic residues.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2007,
25,
677-687)
copyright 2007.
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