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PDBsum entry 1h7h
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Nucleotidyltransferase
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PDB id
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1h7h
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.2.7.7.38
- 3-deoxy-manno-octulosonate cytidylyltransferase.
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Reaction:
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3-deoxy-alpha-D-manno-oct-2-ulosonate + CTP = CMP-3-deoxy-beta-D-manno- octulosonate + diphosphate
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3-deoxy-alpha-D-manno-oct-2-ulosonate
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+
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CTP
Bound ligand (Het Group name = )
matches with 86.21% similarity
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=
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CMP-3-deoxy-beta-D-manno- octulosonate
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+
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diphosphate
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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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J Mol Biol
312:143-155
(2001)
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PubMed id:
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The structure of CMP:2-keto-3-deoxy-manno-octonic acid synthetase and of its complexes with substrates and substrate analogs.
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S.Jelakovic,
G.E.Schulz.
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ABSTRACT
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The enzyme CMP-Kdo synthetase (CKS) catalyzes the activation of the sugar Kdo
(2-keto-3-deoxy-manno-octonic acid) by forming a monophosphate diester. CKS is a
pharmaceutical target because CMP-Kdo is used in the biosynthesis of
lipopolysaccharides that are vital for Gram-negative bacteria. We have refined
the structure of the unligated capsule-specific CKS from Escherichia coli at 1.8
A resolution (1 A=0.1 nm) and we have established the structures of its
complexes with the substrate CTP, with CDP and CMP as well as with the product
analog CMP-NeuAc (CMP-sialate) by X-ray diffraction analyses at resolutions
between 2.1 A and 2.5 A. The N-terminal domains of the dimeric enzyme bind CTP
in a peculiar nucleotide-binding fold, whereas the C-terminal domains form the
dimer interface. The observed binding geometries together with the amino acid
variabilities during evolution and the locations of a putative Mg(2+) and of a
very strongly bound water molecule suggest a pathway for the catalysis. The
N-terminal domain shows sequence homology with the CMP-NeuAc synthetases.
Moreover, the chain fold and the substrate-binding position of CKS resemble
those of other enzymes processing nucleotide-sugars.
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Selected figure(s)
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Figure 3.
Figure 3. Stereo ribbon plot of the CKS dimer viewed along
the molecular 2-fold axis. Subunit B (blue) is at the top. In
the crystals this subunit binds the nucleotides and the analog
CMP-NeuAc (here displayed). The domains are given in different
hues. The exceptional left-handed connection between b6 and b7
is marked red, it connects the two domains. The bulge residues
of b10 are marked by balls.
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Figure 9.
Figure 9. Proposed reaction mechanism of CKS. The b- and
g-phosphates of CTP are bound in the so-called PP-loop. Kdo is
displayed at the position of the NeuAc moiety of bound CMP-NeuAc
without trying to state a contact to a surrounding residue.
During the nucleophilic attack Arg10 moves from the b-phosphate
away to Asp51, and Lys19 moves from the b- to the a-phosphate. A
strongly bound water molecule between the carboxylates of Asp98
and Asp225 is considered to be the base accepting the hydroxyl
proton.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2001,
312,
143-155)
copyright 2001.
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Figures were
selected
by the author.
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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.Plaimas,
R.Eils,
and
R.König
(2010).
Identifying essential genes in bacterial metabolic networks with machine learning methods.
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BMC Syst Biol,
4,
56.
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L.Cipolla,
L.Gabrielli,
D.Bini,
L.Russo,
and
N.Shaikh
(2010).
Kdo: a critical monosaccharide for bacteria viability.
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Nat Prod Rep,
27,
1618-1629.
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L.E.Horsfall,
A.Nelson,
and
A.Berry
(2010).
Identification and characterization of important residues in the catalytic mechanism of CMP-Neu5Ac synthetase from Neisseria meningitidis.
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FEBS J,
277,
2779-2790.
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D.J.Heyes,
C.Levy,
P.Lafite,
I.S.Roberts,
M.Goldrick,
A.V.Stachulski,
S.B.Rossington,
D.Stanford,
S.E.Rigby,
N.S.Scrutton,
and
D.Leys
(2009).
Structure-based mechanism of CMP-2-keto-3-deoxymanno-octulonic acid synthetase: convergent evolution of a sugar-activating enzyme with DNA/RNA polymerases.
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J Biol Chem,
284,
35514-35523.
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PDB codes:
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C.J.Thibodeaux,
C.E.Melançon,
and
H.W.Liu
(2008).
Natural-product sugar biosynthesis and enzymatic glycodiversification.
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Angew Chem Int Ed Engl,
47,
9814-9859.
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H.J.Yoon,
M.J.Ku,
B.Mikami,
and
S.W.Suh
(2008).
Structure of 3-deoxy-manno-octulosonate cytidylyltransferase from Haemophilus influenzae complexed with the substrate 3-deoxy-manno-octulosonate in the beta-configuration.
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Acta Crystallogr D Biol Crystallogr,
64,
1292-1294.
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PDB code:
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J.Liu,
and
A.Mushegian
(2003).
Three monophyletic superfamilies account for the majority of the known glycosyltransferases.
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Protein Sci,
12,
1418-1431.
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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
