4H1I

Structure of human thymidylate synthase at low salt conditions

Summary for 4H1I

• Entry DOI: 10.2210/pdb4h1i/pdb
• Related: 4GYH
• Descriptor: Thymidylate synthase, SULFATE ION (3 entities in total)
• Functional Keywords: nucleotide metabolism, cancer chemotherapy target, methyl transferase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P04818
• Total number of polymer chains: 4
• Total formula weight: 146198.91

Authors

Brunn, N.,Dibrov, S.,Hermann, T. (deposition date: 2012-09-10, release date: 2012-10-03, Last modification date: 2023-09-13)

Primary citation

Brunn, N.D.,Dibrov, S.M.,Kao, M.B.,Ghassemian, M.,Hermann, T.
Analysis of mRNA recognition by human thymidylate synthase.
Biosci.Rep., 34:e00168-e00168, 2014

PubMed Abstract: 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.

PubMed: 25423174
DOI: 10.1042/BSR20140137

Experimental method

X-RAY DIFFRACTION (3.095 Å)