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PDBsum entry 1af7
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Methyltransferase
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PDB id
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1af7
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the chemotaxis receptor methyltransferase cher suggests a conserved structural motif for binding s-Adenosylmethionine.
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Authors
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S.Djordjevic,
A.M.Stock.
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Ref.
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Structure, 1997,
5,
545-558.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Flagellated bacteria swim towards favorable chemicals and away from
deleterious ones. The sensing of chemoeffector gradients involves chemotaxis
receptors, transmembrane proteins that detect stimuli through their periplasmic
domains and transduce signals via their cytoplasmic domains to the downstream
signaling components. Signaling outputs from chemotaxis receptors are influenced
both by the binding of the chemoeffector ligand to the periplasmic domain and by
methylation of specific glutamate residues on the cytoplasmic domain of the
receptor. Methylation is catalyzed by CheR, an S-adenosylmethionine-dependent
methyltransferase. CheR forms a tight complex with the receptor by binding a
region of the receptors that is distinct from the methylation site. CheR belongs
to a broad class of enzymes involved in the methylation of a variety of
substrates. Until now, no structure from the class of protein methyltransferases
has been characterized. RESULTS: The structure of the Salmonella typhimurium
chemotaxis receptor methyltransferase CheR bound to S-adenosylhomocysteine, a
product and inhibitor of the methylation reaction, has been determined at 2.0 A
resolution. The structure reveals CheR to be a two-domain protein, with a
smaller N-terminal helical domain linked through a single polypeptide connection
to a larger C-terminal alpha/beta domain. The C-terminal domain has the
characteristics of a nucleotide-binding fold, with an insertion of a small
antiparallel beta sheet subdomain. The S-adenosylhomocysteine-binding site is
formed mainly by the large domain, with contributions from residues within the
N-terminal domain and the linker region. CONCLUSIONS: The CheR structure shares
some structural similarities with small molecule DNA and RNA methyltransferases,
despite a lack of sequence similarity among them. In particular, there is
significant structural preservation of the S-adenosylmethionine-binding clefts;
the specific length and conformation of a loop in the alpha/beta domain seems to
be required for S-adenosylmethionine binding within these enzymes. Unique
structural features of CheR, such as the beta subdomain, are probably necessary
for CheR's specific interaction with its substrates, the bacterial chemotaxis
receptors.
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Figure 4.
Figure 4. S-adenosylhomocysteine-binding site in CheR. (a)
A stereo diagram (MOLSCRIPT; [57]) of the AdoHcy-binding site.
Only sidechain atoms are included in the figure except for the
residues that form hydrogen bonds with AdoHcy through mainchain
atoms. Hydrogen bonds are represented by dashed lines. (b) A
schematic view of the contacts identified in the crystal
structure of the CheR-AdoHcy complex. Hydrogen bonds are drawn
with dashed lines and covalent bonds are shown as solid lines
connecting the solid spheres that denote atoms. Residues within
the hydrophobic pocket that accommodates the adenine portion of
AdoHcy are represented by parallel curved lines. Sulfur atoms
are shown in green, other atom colors are the same as Figure 2.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1997,
5,
545-558)
copyright 1997.
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