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PDBsum entry 2ckd
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References listed in PDB file
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Key reference
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Title
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The crystal structure of m. Leprae ml2640c defines a large family of putative s-Adenosylmethionine-Dependent methyltransferases in mycobacteria.
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Authors
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M.Graña,
A.Haouz,
A.Buschiazzo,
I.Miras,
A.Wehenkel,
V.Bondet,
W.Shepard,
F.Schaeffer,
S.T.Cole,
P.M.Alzari.
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Ref.
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Protein Sci, 2007,
16,
1896-1904.
[DOI no: ]
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PubMed id
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Abstract
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Mycobacterium leprae protein ML2640c belongs to a large family of conserved
hypothetical proteins predominantly found in mycobacteria, some of them
predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases
(MTase). As part of a Structural Genomics initiative on conserved hypothetical
proteins in pathogenic mycobacteria, we have determined the structure of ML2640c
in two distinct crystal forms. As expected, ML2640c has a typical MTase core
domain and binds the methyl donor substrate AdoMet in a manner consistent with
other known members of this structural family. The putative acceptor
substrate-binding site of ML2640c is a large internal cavity, mostly lined by
aromatic and aliphatic side-chain residues, suggesting that a lipid-like
molecule might be targeted for catalysis. A flap segment (residues 222-256),
which isolates the binding site from the bulk solvent and is highly mobile in
the crystal structures, could serve as a gateway to allow substrate entry and
product release. The multiple sequence alignment of ML2640c-like proteins
revealed that the central alpha/beta core and the AdoMet-binding site are very
well conserved within the family. However, the amino acid positions defining the
binding site for the acceptor substrate display a higher variability, suggestive
of distinct acceptor substrate specificities. The ML2640c crystal structures
offer the first structural glimpses at this important family of mycobacterial
proteins and lend strong support to their functional assignment as
AdoMet-dependent methyltransferases.
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Figure 2.
Figure 2. (A) Structural superposition (RMSD 2.1 Å for 221 aligned residues) of the protein backbones of ML2640c (light brown) and
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Figure 3.
Figure 3. (A) Residue conservation from the multiple alignment of ML2640c-like sequences (Supplemental Fig. 1) mapped onto the
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The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(2007,
16,
1896-1904)
copyright 2007.
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