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PDBsum entry 1ukd
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Nucleotide monophosphate kinase
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PDB id
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1ukd
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Enzyme class:
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E.C.2.7.4.14
- UMP/CMP kinase.
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Reaction:
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1.
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CMP + ATP = CDP + ADP
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2.
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dCMP + ATP = dCDP + ADP
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3.
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UMP + ATP = UDP + ADP
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Biochemistry
35:9716-9727
(1996)
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PubMed id:
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Crystal structure of the complex of UMP/CMP kinase from Dictyostelium discoideum and the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-uridyl) pentaphosphate (UP5A) and Mg2+ at 2.2 A: implications for water-mediated specificity.
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K.Scheffzek,
W.Kliche,
L.Wiesmüller,
J.Reinstein.
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ABSTRACT
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The three-dimensional structure of the UMP/CMP kinase (UK) from the slime mold
Dictyostelium discoideum complexed with the specific and asymmetric bisubstrate
inhibitor P1-(5'-adenosyl) P5-(5'-uridyl) pentaphosphate (UP5A) has been
determined at a resolution of 2.2 A. The structure of the enzyme, which has up
to 41% sequence homology with known adenylate kinases (AK), represents a closed
conformation with the flexible monophosphate binding domain (NMP site) being
closed over the uridyl moiety of the dinucleotide. Two water molecules were
found within hydrogen-bonding distance to the uracil base. The key residue for
the positioning and stabilization of those water molecules appears to be
asparagine 97, a residue that is highly specific for AK-homologous UMP kinases,
but is almost invariably a glutamine in adenylate kinases. Other residues in
this region are highly conserved among AK-related NMP kinases. The catalytic
Mg2+ ion is coordinated with octahedral geometry to four water molecules and two
oxygens of the phosphate chain of UP5A but has no direct interactions with the
protein. The comparison of the geometry of the UKdicty.UP5A.Mg2+ complex with
the previously reported structure of the UKyeast.ADP.ADP complex
[Müller-Dieckmann & Schulz (1994) J. Mol. Biol. 236, 361-367] suggests that
UP5A in our structure mimics an ADP.Mg.UDP biproduct inhibitor rather than an
ATP. MG.UMP bisubstrate inhibitor.
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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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G.Walia,
K.Gajendar,
and
A.Surolia
(2011).
Identification of critical residues of the mycobacterial dephosphocoenzyme a kinase by site-directed mutagenesis.
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PLoS One,
6,
e15228.
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N.Stern,
D.T.Major,
H.E.Gottlieb,
D.Weizman,
and
B.Fischer
(2010).
What is the conformation of physiologically-active dinucleoside polyphosphates in solution? Conformational analysis of free dinucleoside polyphosphates by NMR and molecular dynamics simulations.
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Org Biomol Chem,
8,
4637-4652.
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R.B.Stockbridge,
and
R.Wolfenden
(2009).
The intrinsic reactivity of ATP and the catalytic proficiencies of kinases acting on glucose, N-acetylgalactosamine, and homoserine: a thermodynamic analysis.
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J Biol Chem,
284,
22747-22757.
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A.Ofiteru,
N.Bucurenci,
E.Alexov,
T.Bertrand,
P.Briozzo,
H.Munier-Lehmann,
and
A.M.Gilles
(2007).
Structural and functional consequences of single amino acid substitutions in the pyrimidine base binding pocket of Escherichia coli CMP kinase.
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FEBS J,
274,
3363-3373.
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PDB codes:
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D.Topalis,
H.Kumamoto,
M.F.Amaya Velasco,
L.Dugué,
A.Haouz,
J.A.Alexandre,
S.Gallois-Montbrun,
P.M.Alzari,
S.Pochet,
L.A.Agrofoglio,
and
D.Deville-Bonne
(2007).
Nucleotide binding to human UMP-CMP kinase using fluorescent derivatives -- a screening based on affinity for the UMP-CMP binding site.
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FEBS J,
274,
3704-3714.
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J.A.Alexandre,
B.Roy,
D.Topalis,
S.Pochet,
C.Périgaud,
and
D.Deville-Bonne
(2007).
Enantioselectivity of human AMP, dTMP and UMP-CMP kinases.
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Nucleic Acids Res,
35,
4895-4904.
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M.Kotaka,
B.Dhaliwal,
J.Ren,
C.E.Nichols,
R.Angell,
M.Lockyer,
A.R.Hawkins,
and
D.K.Stammers
(2006).
Structures of S. aureus thymidylate kinase reveal an atypical active site configuration and an intermediate conformational state upon substrate binding.
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Protein Sci,
15,
774-784.
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PDB codes:
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M.L.Ginger,
E.S.Ngazoa,
C.A.Pereira,
T.J.Pullen,
M.Kabiri,
K.Becker,
K.Gull,
and
D.Steverding
(2005).
Intracellular positioning of isoforms explains an unusually large adenylate kinase gene family in the parasite Trypanosoma brucei.
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J Biol Chem,
280,
11781-11789.
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P.Briozzo,
C.Evrin,
P.Meyer,
L.Assairi,
N.Joly,
O.Barzu,
and
A.M.Gilles
(2005).
Structure of Escherichia coli UMP kinase differs from that of other nucleoside monophosphate kinases and sheds new light on enzyme regulation.
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J Biol Chem,
280,
25533-25540.
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PDB codes:
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D.Segura-Peña,
N.Sekulic,
S.Ort,
M.Konrad,
and
A.Lavie
(2004).
Substrate-induced conformational changes in human UMP/CMP kinase.
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J Biol Chem,
279,
33882-33889.
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PDB code:
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N.Fernandez-Fuentes,
A.Hermoso,
J.Espadaler,
E.Querol,
F.X.Aviles,
and
B.Oliva
(2004).
Classification of common functional loops of kinase super-families.
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Proteins,
56,
539-555.
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A.Haouz,
V.Vanheusden,
H.Munier-Lehmann,
M.Froeyen,
P.Herdewijn,
S.Van Calenbergh,
and
M.Delarue
(2003).
Enzymatic and structural analysis of inhibitors designed against Mycobacterium tuberculosis thymidylate kinase. New insights into the phosphoryl transfer mechanism.
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J Biol Chem,
278,
4963-4971.
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PDB codes:
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C.Gagyi,
N.Bucurenci,
O.Sîrbu,
G.Labesse,
M.Ionescu,
A.Ofiteru,
L.Assairi,
S.Landais,
A.Danchin,
O.Bârzu,
and
A.M.Gilles
(2003).
UMP kinase from the Gram-positive bacterium Bacillus subtilis is strongly dependent on GTP for optimal activity.
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Eur J Biochem,
270,
3196-3204.
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C.Pasti,
S.Gallois-Montbrun,
H.Munier-Lehmann,
M.Veron,
A.M.Gilles,
and
D.Deville-Bonne
(2003).
Reaction of human UMP-CMP kinase with natural and analog substrates.
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Eur J Biochem,
270,
1784-1790.
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L.Yu,
J.Mack,
P.J.Hajduk,
S.J.Kakavas,
A.Y.Saiki,
C.G.Lerner,
and
E.T.Olejniczak
(2003).
Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae.
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Protein Sci,
12,
2613-2621.
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PDB code:
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N.Sekulic,
L.Shuvalova,
O.Spangenberg,
M.Konrad,
and
A.Lavie
(2002).
Structural characterization of the closed conformation of mouse guanylate kinase.
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J Biol Chem,
277,
30236-30243.
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PDB code:
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S.K.Singh,
O.V.Kurnasov,
B.Chen,
H.Robinson,
N.V.Grishin,
A.L.Osterman,
and
H.Zhang
(2002).
Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
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J Biol Chem,
277,
33291-33299.
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PDB code:
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B.C.Low,
K.T.Seow,
and
G.R.Guy
(2000).
Evidence for a novel Cdc42GAP domain at the carboxyl terminus of BNIP-2.
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J Biol Chem,
275,
14415-14422.
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I.M.Li de La Sierra,
J.Gallay,
M.Vincent,
T.Bertrand,
P.Briozzo,
O.Bârzu,
and
A.M.Gilles
(2000).
Substrate-induced fit of the ATP binding site of cytidine monophosphate kinase from Escherichia coli: time-resolved fluorescence of 3'-anthraniloyl-2'-deoxy-ADP and molecular modeling.
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Biochemistry,
39,
15870-15878.
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M.C.Hutter,
and
V.Helms
(2000).
Phosphoryl transfer by a concerted reaction mechanism in UMP/CMP-kinase.
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Protein Sci,
9,
2225-2231.
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N.Ostermann,
I.Schlichting,
R.Brundiers,
M.Konrad,
J.Reinstein,
T.Veit,
R.S.Goody,
and
A.Lavie
(2000).
Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate.
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Structure,
8,
629-642.
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PDB codes:
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M.G.Rudolph,
T.J.Veit,
and
J.Reinstein
(1999).
The novel fluorescent CDP-analogue (Pbeta)MABA-CDP is a specific probe for the NMP binding site of UMP/CMP kinase.
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Protein Sci,
8,
2697-2704.
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M.Gruen,
C.Becker,
A.Beste,
J.Reinstein,
A.J.Scheidig,
and
R.S.Goody
(1999).
2'Halo-ATP and -GTP analogues: rational phasing tools for protein crystallography.
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Protein Sci,
8,
2524-2528.
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R.C.Hillig,
L.Renault,
I.R.Vetter,
T.Drell,
A.Wittinghofer,
and
J.Becker
(1999).
The crystal structure of rna1p: a new fold for a GTPase-activating protein.
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Mol Cell,
3,
781-791.
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PDB code:
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A.Lavie,
M.Konrad,
R.Brundiers,
R.S.Goody,
I.Schlichting,
and
J.Reinstein
(1998).
Crystal structure of yeast thymidylate kinase complexed with the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-thymidyl) pentaphosphate (TP5A) at 2.0 A resolution: implications for catalysis and AZT activation.
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Biochemistry,
37,
3677-3686.
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PDB code:
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A.Lavie,
N.Ostermann,
R.Brundiers,
R.S.Goody,
J.Reinstein,
M.Konrad,
and
I.Schlichting
(1998).
Structural basis for efficient phosphorylation of 3'-azidothymidine monophosphate by Escherichia coli thymidylate kinase.
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Proc Natl Acad Sci U S A,
95,
14045-14050.
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PDB codes:
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A.Matte,
L.W.Tari,
and
L.T.Delbaere
(1998).
How do kinases transfer phosphoryl groups?
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Structure,
6,
413-419.
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L.McFail-Isom,
X.Shui,
and
L.D.Williams
(1998).
Divalent cations stabilize unstacked conformations of DNA and RNA by interacting with base pi systems.
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Biochemistry,
37,
17105-17111.
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M.B.Berry,
and
G.N.Phillips
(1998).
Crystal structures of Bacillus stearothermophilus adenylate kinase with bound Ap5A, Mg2+ Ap5A, and Mn2+ Ap5A reveal an intermediate lid position and six coordinate octahedral geometry for bound Mg2+ and Mn2+.
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Proteins,
32,
276-288.
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PDB codes:
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N.Bucurenci,
L.Serina,
C.Zaharia,
S.Landais,
A.Danchin,
and
O.Bârzu
(1998).
Mutational analysis of UMP kinase from Escherichia coli.
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J Bacteriol,
180,
473-477.
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P.Briozzo,
B.Golinelli-Pimpaneau,
A.M.Gilles,
J.F.Gaucher,
S.Burlacu-Miron,
H.Sakamoto,
J.Janin,
and
O.Bârzu
(1998).
Structures of escherichia coli CMP kinase alone and in complex with CDP: a new fold of the nucleoside monophosphate binding domain and insights into cytosine nucleotide specificity.
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Structure,
6,
1517-1527.
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PDB codes:
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I.Schlichting,
and
J.Reinstein
(1997).
Structures of active conformations of UMP kinase from Dictyostelium discoideum suggest phosphoryl transfer is associative.
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Biochemistry,
36,
9290-9296.
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PDB codes:
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K.Wild,
R.Grafmüller,
E.Wagner,
and
G.E.Schulz
(1997).
Structure, catalysis and supramolecular assembly of adenylate kinase from maize.
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Eur J Biochem,
250,
326-331.
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PDB code:
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K.Wild,
T.Bohner,
G.Folkers,
and
G.E.Schulz
(1997).
The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue.
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Protein Sci,
6,
2097-2106.
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PDB codes:
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P.Haney,
J.Konisky,
K.K.Koretke,
Z.Luthey-Schulten,
and
P.G.Wolynes
(1997).
Structural basis for thermostability and identification of potential active site residues for adenylate kinases from the archaeal genus Methanococcus.
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Proteins,
28,
117-130.
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Y.Zhang,
Y.Li,
Y.Wu,
and
H.Yan
(1997).
Structural and functional roles of tyrosine 78 of yeast guanylate kinase.
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J Biol Chem,
272,
19343-19350.
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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
codes are
shown on the right.
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Links
