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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Co-crystal structure of znf ubp domain from the deubiquitinating enzyme isopeptidase t (isot) in complex with ubiquitin
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Structure:
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Ubiquitin carboxyl-terminal hydrolase 5. Chain: a, d. Fragment: the znf ubp domain of isot (residues 163-291). Synonym: ubiquitin thiolesterase 5, ubiquitin-specific processing protease 5, deubiquitinating enzyme 5, isopeptidase t. Engineered: yes. Ubiquitin. Chain: b, e. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: usp5, isot. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
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Biol. unit:
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Octamer (from
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Resolution:
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1.99Å
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R-factor:
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0.229
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R-free:
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0.268
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Authors:
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F.E.Reyes-Turcu,J.R.Horton,J.E.Mullally,A.Heroux,X.Cheng, K.D.Wilkinson
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Key ref:
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F.E.Reyes-Turcu
et al.
(2006).
The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin.
Cell,
124,
1197-1208.
PubMed id:
DOI:
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Date:
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21-Feb-06
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Release date:
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04-Apr-06
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PROCHECK
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Headers
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References
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Enzyme class:
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Chains A, D:
E.C.3.4.19.12
- ubiquitinyl hydrolase 1.
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Reaction:
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Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
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DOI no:
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Cell
124:1197-1208
(2006)
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PubMed id:
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The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin.
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F.E.Reyes-Turcu,
J.R.Horton,
J.E.Mullally,
A.Heroux,
X.Cheng,
K.D.Wilkinson.
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ABSTRACT
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Ubiquitin binding proteins regulate the stability, function, and/or localization
of ubiquitinated proteins. Here we report the crystal structures of the
zinc-finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme
isopeptidase T (IsoT, or USP5) alone and in complex with ubiquitin. Unlike other
ubiquitin binding domains, this domain contains a deep binding pocket where the
C-terminal diglycine motif of ubiquitin is inserted, thus explaining the
specificity of IsoT for an unmodified C terminus on the proximal subunit of
polyubiquitin. Mutations in the domain demonstrate that it is required for
optimal catalytic activation of IsoT. This domain is present in several other
protein families, and the ZnF UBP domain from an E3 ligase also requires the C
terminus of ubiquitin for binding. These data suggest that binding the ubiquitin
C terminus may be necessary for the function of other proteins.
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Selected figure(s)
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Figure 3.
Figure 3. Structure of IsoT ZnF UBP Domain Bound to
Ubiquitin
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Figure 4.
Figure 4. Interaction between Conserved Residues of the ZnF
UBP Domain of IsoT and Ubiquitin
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2006,
124,
1197-1208)
copyright 2006.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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K.Y.Huang,
G.A.Amodeo,
L.Tong,
and
A.McDermott
(2011).
The structure of human ubiquitin in 2-methyl-2,4-pentanediol: a new conformational switch.
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Protein Sci,
20,
630-639.
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PDB code:
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A.Bremm,
S.M.Freund,
and
D.Komander
(2010).
Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne.
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Nat Struct Mol Biol,
17,
939-947.
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PDB code:
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A.Köhler,
E.Zimmerman,
M.Schneider,
E.Hurt,
and
N.Zheng
(2010).
Structural basis for assembly and activation of the heterotetrameric SAGA histone H2B deubiquitinase module.
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Cell,
141,
606-617.
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PDB code:
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A.Schmidt,
M.Hagen,
E.Schütze,
A.Schmidt,
and
E.Kothe
(2010).
In silico prediction of potential metallothioneins and metallohistins in actinobacteria.
|
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J Basic Microbiol,
50,
562-569.
|
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|
|
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|
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A.X.Song,
C.J.Zhou,
X.Guan,
K.H.Sze,
and
H.Y.Hu
(2010).
Solution structure of the N-terminal domain of DC-UbP/UBTD2 and its interaction with ubiquitin.
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Protein Sci,
19,
1104-1109.
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PDB code:
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E.J.Bennett,
and
J.W.Harper
(2010).
Ubiquitin gets CARDed.
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Cell,
141,
220-222.
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J.M.Winget,
and
T.Mayor
(2010).
The diversity of ubiquitin recognition: hot spots and varied specificity.
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Mol Cell,
38,
627-635.
|
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|
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M.Drag,
and
G.S.Salvesen
(2010).
Emerging principles in protease-based drug discovery.
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Nat Rev Drug Discov,
9,
690-701.
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N.L.Samara,
A.B.Datta,
C.E.Berndsen,
X.Zhang,
T.Yao,
R.E.Cohen,
and
C.Wolberger
(2010).
Structural insights into the assembly and function of the SAGA deubiquitinating module.
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Science,
328,
1025-1029.
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PDB codes:
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S.Virdee,
Y.Ye,
D.P.Nguyen,
D.Komander,
and
J.W.Chin
(2010).
Engineered diubiquitin synthesis reveals Lys29-isopeptide specificity of an OTU deubiquitinase.
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Nat Chem Biol,
6,
750-757.
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PDB code:
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W.Zeng,
L.Sun,
X.Jiang,
X.Chen,
F.Hou,
A.Adhikari,
M.Xu,
and
Z.J.Chen
(2010).
Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity.
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Cell,
141,
315-330.
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A.Ramanathan,
and
P.K.Agarwal
(2009).
Computational identification of slow conformational fluctuations in proteins.
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J Phys Chem B,
113,
16669-16680.
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D.Komander,
M.J.Clague,
and
S.Urbé
(2009).
Breaking the chains: structure and function of the deubiquitinases.
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Nat Rev Mol Cell Biol,
10,
550-563.
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|
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F.E.Reyes-Turcu,
and
K.D.Wilkinson
(2009).
Polyubiquitin binding and disassembly by deubiquitinating enzymes.
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Chem Rev,
109,
1495-1508.
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F.E.Reyes-Turcu,
K.H.Ventii,
and
K.D.Wilkinson
(2009).
Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes.
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Annu Rev Biochem,
78,
363-397.
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H.B.Kamadurai,
J.Souphron,
D.C.Scott,
D.M.Duda,
D.J.Miller,
D.Stringer,
R.C.Piper,
and
B.A.Schulman
(2009).
Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex.
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Mol Cell,
36,
1095-1102.
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PDB codes:
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I.Dikic,
S.Wakatsuki,
and
K.J.Walters
(2009).
Ubiquitin-binding domains - from structures to functions.
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Nat Rev Mol Cell Biol,
10,
659-671.
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K.Iwai,
and
F.Tokunaga
(2009).
Linear polyubiquitination: a new regulator of NF-kappaB activation.
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EMBO Rep,
10,
706-713.
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|
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L.Tian,
X.Wu,
Y.Lin,
Z.Liu,
F.Xiong,
Z.Han,
Y.Zhou,
Q.Zeng,
Y.Wang,
J.Deng,
and
H.Chen
(2009).
Characterization and potential function of a novel pre-implantation embryo-specific RING finger protein: TRIML1.
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Mol Reprod Dev,
76,
656-664.
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S.A.Matheny,
and
M.A.White
(2009).
Signaling Threshold Regulation by the Ras Effector IMP.
|
| |
J Biol Chem,
284,
11007-11011.
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S.Dayal,
A.Sparks,
J.Jacob,
N.Allende-Vega,
D.P.Lane,
and
M.K.Saville
(2009).
Suppression of the Deubiquitinating Enzyme USP5 Causes the Accumulation of Unanchored Polyubiquitin and the Activation of p53.
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J Biol Chem,
284,
5030-5041.
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W.Li,
D.Tu,
L.Li,
T.Wollert,
R.Ghirlando,
A.T.Brunger,
and
Y.Ye
(2009).
Mechanistic insights into active site-associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2.
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Proc Natl Acad Sci U S A,
106,
3722-3727.
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PDB code:
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Z.P.Xia,
L.Sun,
X.Chen,
G.Pineda,
X.Jiang,
A.Adhikari,
W.Zeng,
and
Z.J.Chen
(2009).
Direct activation of protein kinases by unanchored polyubiquitin chains.
|
| |
Nature,
461,
114-119.
|
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|
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|
|
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A.Gonçalves,
E.Charafe-Jauffret,
F.Bertucci,
S.Audebert,
Y.Toiron,
B.Esterni,
F.Monville,
C.Tarpin,
J.Jacquemier,
G.Houvenaeghel,
C.Chabannon,
J.M.Extra,
P.Viens,
J.P.Borg,
and
D.Birnbaum
(2008).
Protein profiling of human breast tumor cells identifies novel biomarkers associated with molecular subtypes.
|
| |
Mol Cell Proteomics,
7,
1420-1433.
|
|
|
|
|
|
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B.J.Winborn,
S.M.Travis,
S.V.Todi,
K.M.Scaglione,
P.Xu,
A.J.Williams,
R.E.Cohen,
J.Peng,
and
H.L.Paulson
(2008).
The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains.
|
| |
J Biol Chem,
283,
26436-26443.
|
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B.Nicholson,
C.A.Leach,
S.J.Goldenberg,
D.M.Francis,
M.P.Kodrasov,
X.Tian,
J.Shanks,
D.E.Sterner,
A.Bernal,
M.R.Mattern,
K.D.Wilkinson,
and
T.R.Butt
(2008).
Characterization of ubiquitin and ubiquitin-like-protein isopeptidase activities.
|
| |
Protein Sci,
17,
1035-1043.
|
|
|
|
|
|
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E.Meulmeester,
M.Kunze,
H.H.Hsiao,
H.Urlaub,
and
F.Melchior
(2008).
Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25.
|
| |
Mol Cell,
30,
610-619.
|
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|
|
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F.E.Reyes-Turcu,
J.R.Shanks,
D.Komander,
and
K.D.Wilkinson
(2008).
Recognition of polyubiquitin isoforms by the multiple ubiquitin binding modules of isopeptidase T.
|
| |
J Biol Chem,
283,
19581-19592.
|
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J.Bonnet,
C.Romier,
L.Tora,
and
D.Devys
(2008).
Zinc-finger UBPs: regulators of deubiquitylation.
|
| |
Trends Biochem Sci,
33,
369-375.
|
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|
|
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L.Song,
and
M.Rape
(2008).
Reverse the curse--the role of deubiquitination in cell cycle control.
|
| |
Curr Opin Cell Biol,
20,
156-163.
|
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|
|
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M.Drag,
and
G.S.Salvesen
(2008).
DeSUMOylating enzymes--SENPs.
|
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IUBMB Life,
60,
734-742.
|
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|
|
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|
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M.Drag,
J.Mikolajczyk,
M.Bekes,
F.E.Reyes-Turcu,
J.A.Ellman,
K.D.Wilkinson,
and
G.S.Salvesen
(2008).
Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes).
|
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Biochem J,
415,
367-375.
|
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M.J.Clague,
J.M.Coulson,
and
S.Urbé
(2008).
Deciphering histone 2A deubiquitination.
|
| |
Genome Biol,
9,
202.
|
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O.Okhrimenko,
and
I.Jelesarov
(2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
|
| |
J Mol Recognit,
21,
1.
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T.E.Messick,
N.S.Russell,
A.J.Iwata,
K.L.Sarachan,
R.Shiekhattar,
J.R.Shanks,
F.E.Reyes-Turcu,
K.D.Wilkinson,
and
R.Marmorstein
(2008).
Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein.
|
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J Biol Chem,
283,
11038-11049.
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PDB codes:
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Y.Sato,
A.Yoshikawa,
A.Yamagata,
H.Mimura,
M.Yamashita,
K.Ookata,
O.Nureki,
K.Iwai,
M.Komada,
and
S.Fukai
(2008).
Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains.
|
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Nature,
455,
358-362.
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PDB codes:
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A.Catic,
E.Fiebiger,
G.A.Korbel,
D.Blom,
P.J.Galardy,
and
H.L.Ploegh
(2007).
Screen for ISG15-crossreactive deubiquitinases.
|
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PLoS ONE,
2,
e679.
|
|
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|
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A.Fernández-Montalván,
T.Bouwmeester,
G.Joberty,
R.Mader,
M.Mahnke,
B.Pierrat,
J.M.Schlaeppi,
S.Worpenberg,
and
B.Gerhartz
(2007).
Biochemical characterization of USP7 reveals post-translational modification sites and structural requirements for substrate processing and subcellular localization.
|
| |
FEBS J,
274,
4256-4270.
|
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B.C.Dickinson,
R.Varadan,
and
D.Fushman
(2007).
Effects of cyclization on conformational dynamics and binding properties of Lys48-linked di-ubiquitin.
|
| |
Protein Sci,
16,
369-378.
|
|
|
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|
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F.Nicassio,
N.Corrado,
J.H.Vissers,
L.B.Areces,
S.Bergink,
J.A.Marteijn,
B.Geverts,
A.B.Houtsmuller,
W.Vermeulen,
P.P.Di Fiore,
and
E.Citterio
(2007).
Human USP3 is a chromatin modifier required for S phase progression and genome stability.
|
| |
Curr Biol,
17,
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H.Barriere,
C.Nemes,
K.Du,
and
G.L.Lukacs
(2007).
Plasticity of polyubiquitin recognition as lysosomal targeting signals by the endosomal sorting machinery.
|
| |
Mol Biol Cell,
18,
3952-3965.
|
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|
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|
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M.D.Allen,
and
M.Bycroft
(2007).
The solution structure of the ZnF UBP domain of USP33/VDU1.
|
| |
Protein Sci,
16,
2072-2075.
|
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PDB code:
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|
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M.G.Bomar,
M.T.Pai,
S.R.Tzeng,
S.S.Li,
and
P.Zhou
(2007).
Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta.
|
| |
EMBO Rep,
8,
247-251.
|
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PDB code:
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|
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M.T.Pai,
S.R.Tzeng,
J.J.Kovacs,
M.A.Keaton,
S.S.Li,
T.P.Yao,
and
P.Zhou
(2007).
Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin.
|
| |
J Mol Biol,
370,
290-302.
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PDB code:
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T.Woelk,
S.Sigismund,
L.Penengo,
and
S.Polo
(2007).
The ubiquitination code: a signalling problem.
|
| |
Cell Div,
2,
11.
|
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A.Amerik,
N.Sindhi,
and
M.Hochstrasser
(2006).
A conserved late endosome-targeting signal required for Doa4 deubiquitylating enzyme function.
|
| |
J Cell Biol,
175,
825-835.
|
|
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C.Boyault,
B.Gilquin,
Y.Zhang,
V.Rybin,
E.Garman,
W.Meyer-Klaucke,
P.Matthias,
C.W.Müller,
and
S.Khochbin
(2006).
HDAC6-p97/VCP controlled polyubiquitin chain turnover.
|
| |
EMBO J,
25,
3357-3366.
|
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C.Raiborg,
T.Slagsvold,
and
H.Stenmark
(2006).
A new side to ubiquitin.
|
| |
Trends Biochem Sci,
31,
541-544.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
