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PDBsum entry 4gyh
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References listed in PDB file
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Key reference
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Title
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Analysis of mRNA recognition by human thymidylate synthase.
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Authors
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N.D.Brunn,
S.M.Dibrov,
M.B.Kao,
M.Ghassemian,
T.Hermann.
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Ref.
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Biosci Rep, 2014,
34,
e00168.
[DOI no: ]
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PubMed id
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Abstract
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Expression of hTS (human thymidylate synthase), a key enzyme in thymidine
biosynthesis, is regulated on the translational level through a feedback
mechanism that is rarely found in eukaryotes. At low substrate concentrations,
the ligand-free enzyme binds to its own mRNA and stabilizes a hairpin structure
that sequesters the start codon. When in complex with dUMP
(2'-deoxyuridine-5'-monophosphate) and a THF (tetrahydrofolate) cofactor, the
enzyme adopts a conformation that is unable to bind and repress expression of
mRNA. Here, we have used a combination of X-ray crystallography, RNA mutagenesis
and site-specific cross-linking studies to investigate the molecular recognition
of TS mRNA by the hTS enzyme. The interacting mRNA region was narrowed to the
start codon and immediately flanking sequences. In the hTS enzyme, a
helix-loop-helix domain on the protein surface was identified as the putative
RNA-binding site.
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