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PDBsum entry 1gqc
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Catalytic mechanism of cmp:2-Keto-3-Deoxy-Manno-Octonic acid synthetase as derived from complexes with reaction educt and product.
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Authors
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S.Jelakovic,
G.E.Schulz.
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Ref.
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Biochemistry, 2002,
41,
1174-1181.
[DOI no: ]
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PubMed id
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Abstract
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The activation of the sugar 2-keto-3-deoxy-manno-octonic acid (Kdo) is catalyzed
by CMP-Kdo synthetase (EC 2.7.7.38) and results in a monophosphate diester with
CMP. The enzyme is a pharmaceutical target because CMP-Kdo is required for the
biosynthesis of lipopolysaccharides that are vital for Gram-negative bacteria.
We have established the structures of an enzyme complex with the educt CTP and
of a complex with the product CMP-Kdo by X-ray diffraction analyses at 100 K,
both at 2.6 A resolution. The N-terminal domains of the dimeric enzyme bind CTP
in a peculiar nucleotide-binding fold with the beta- and gamma-phosphates
located at the so-called "PP-loop", whereas the C-terminal domains participate
in Kdo binding and in the dimer interface. The unstable nucleotide-sugar CMP-Kdo
was produced in a crystal and stabilized by freezing to 100 K. Its formation is
accompanied by an induced fit involving mainchain displacements in the 2 A
range. The observed binding conformations together with the amino acid
conservation pattern during evolution and the putative location of the required
Mg(2+) ion suggest a reaction pathway. The enzyme is structurally homologous to
the CMP-N-acetylneuraminic acid synthetases in all parts except for the dimer
interface. Moreover, the chainfold and the substrate-binding positions resemble
those of other enzymes processing nucleotide sugars.
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Secondary reference #1
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Title
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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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Authors
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S.Jelakovic,
G.E.Schulz.
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Ref.
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J Mol Biol, 2001,
312,
143-155.
[DOI no: ]
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PubMed id
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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
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #2
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Title
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The three-Dimensional structure of capsule-Specific cmp: 2-Keto-3-Deoxy-Manno-Octonic acid synthetase from escherichia coli.
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Authors
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S.Jelakovic,
K.Jann,
G.E.Schulz.
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Ref.
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FEBS Lett, 1996,
391,
157-161.
[DOI no: ]
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PubMed id
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