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* Residue conservation analysis
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Enzyme class:
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E.C.6.3.2.19
- Ubiquitin--protein ligase.
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Reaction:
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ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine
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ATP
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+
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ubiquitin
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+
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protein lysine
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=
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AMP
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+
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diphosphate
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+
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protein N-ubiquityllysine
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Biological process
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regulation of protein metabolic process
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6 terms
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Biochemical function
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nucleotide binding
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6 terms
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DOI no:
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J Mol Biol
344:513-526
(2004)
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PubMed id:
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Solution structure of the ubiquitin-conjugating enzyme UbcH5B.
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K.Houben,
C.Dominguez,
F.M.van Schaik,
H.T.Timmers,
A.M.Bonvin,
R.Boelens.
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ABSTRACT
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The ubiquitination pathway is the main pathway for protein degradation in
eukaryotic cells. The attachment of ubiquitin to a substrate protein is
catalyzed by three types of enzymes, namely a ubiquitin activating enzyme (E1),
a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). Here, the
structure of the human ubiquitin-conjugating enzyme (E2) UbcH5B has been solved
by a combination of homology modeling, NMR relaxation data and automated NOE
assignments. Comparison to E2 structures solved previously by X-ray
crystallography or NMR shows in all cases the same compact fold, but differences
are observed in the orientation of both N and C-terminal alpha-helices. The
N-terminal helix that is involved in binding to ubiquitin ligases (E3) displays
a different position, which could have consequences for precise E2-E3
recognition. In addition, multiple conformations of the side-chain of Asn77 are
found in solution, which contrasts the single hydrogen-bonded conformation in
the crystal structures of E2 enzymes. The possible implication of this
conformational freedom of Asn77 for its catalytic function is discussed.
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Selected figure(s)
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Figure 6.
Figure 6. Overlay of the UbcH5B and yeast Ubc4 structures
(PDB: 1QCQ). The Figure shows the differential positions of
helix H1, H3 and H4 in the two structures. UbcH5B is displayed
blue and Ubc4 in white. This Figure was generated with the
program MOLMOL.65
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Figure 7.
Figure 7. Comparison of the position of the asparagine
residue important for oxyanion stabilization in E2-catalyzed
ubiquitin conjugation. Left: NMR ensemble of UbcH5B structures
(ten structures). Right: Overlay of eight E2 X-ray structures
(PDB-codes: 1QCQ, 1A3S, 1AYZ, 1FZY, 1U9A, 2AAK, 2UCZ, 2EZC).
This Figure was generated with the programs Molscript66 and
Raster3D.67
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2004,
344,
513-526)
copyright 2004.
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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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A.G.Eldridge,
and
T.O'Brien
(2010).
Therapeutic strategies within the ubiquitin proteasome system.
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Cell Death Differ, 17,
4.
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D.M.Wenzel,
K.E.Stoll,
and
R.E.Klevit
(2010).
E2s: structurally economical and functionally replete.
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Biochem J, 433,
31-42.
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T.Ju,
W.Bocik,
A.Majumdar,
and
J.R.Tolman
(2010).
Solution structure and dynamics of human ubiquitin conjugating enzyme Ube2g2.
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Proteins, 78,
1291-1301.
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PDB code:
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L.K.Bailey,
L.J.Campbell,
K.A.Evetts,
K.Littlefield,
E.Rajendra,
D.Nietlispach,
D.Owen,
and
H.R.Mott
(2009).
The Structure of Binder of Arl2 (BART) Reveals a Novel G Protein Binding Domain: IMPLICATIONS FOR FUNCTION.
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J Biol Chem, 284,
992-999.
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PDB code:
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S.Rehm,
S.Han,
I.Hassani,
A.Sokocevic,
H.R.Jonker,
J.W.Engels,
and
H.Schwalbe
(2009).
The high resolution NMR structure of parvulustat (Z-2685) from Streptomyces parvulus FH-1641: comparison with tendamistat from Streptomyces tendae 4158.
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Chembiochem, 10,
119-127.
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PDB code:
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A.U.Singer,
J.R.Rohde,
R.Lam,
T.Skarina,
O.Kagan,
R.Dileo,
N.Y.Chirgadze,
M.E.Cuff,
A.Joachimiak,
M.Tyers,
P.J.Sansonetti,
C.Parsot,
and
A.Savchenko
(2008).
Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases.
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Nat Struct Mol Biol, 15,
1293-1301.
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PDB code:
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C.Stordeur,
R.Dallüge,
O.Birkenmeier,
H.Wienk,
R.Rudolph,
C.Lange,
and
C.Lücke
(2008).
The NMR solution structure of the artificial protein M7 matches the computationally designed model.
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Proteins, 72,
1104-1107.
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PDB code:
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Z.Xu,
E.Kohli,
K.I.Devlin,
M.Bold,
J.C.Nix,
and
S.Misra
(2008).
Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes.
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BMC Struct Biol, 8,
26.
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PDB code:
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N.Sibille,
A.Favier,
A.I.Azuaga,
G.Ganshaw,
R.Bott,
A.M.Bonvin,
R.Boelens,
and
N.A.van Nuland
(2006).
Comparative NMR study on the impact of point mutations on protein stability of Pseudomonas mendocina lipase.
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Protein Sci, 15,
1915-1927.
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H.Wienk,
S.Tomaselli,
C.Bernard,
R.Spurio,
D.Picone,
C.O.Gualerzi,
and
R.Boelens
(2005).
Solution structure of the C1-subdomain of Bacillus stearothermophilus translation initiation factor IF2.
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Protein Sci, 14,
2461-2468.
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PDB code:
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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
