PDBsum entry 4gyh

Transferase

PDB id: 4gyh

Contents

Protein chain

263 a.a.

Ligands

SO4 ×2

PDB id:

4gyh

Name:

Transferase

Title:

Structure of human thymidylate synthase at high salt conditions

Structure:

Thymidylate synthase. Chain: a. Synonym: ts, tsase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tyms, ts, ok/sw-cl.29. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

3.01Å R-factor: 0.222 R-free: 0.280

Authors:

N.Brunn,S.Dibrov,T.Hermann

Key ref:

N.D.Brunn et al. (2014). Analysis of mRNA recognition by human thymidylate synthase. Biosci Rep, 34, e00168. PubMed id: 25423174 DOI: 10.1042/BSR20140137

Date:

05-Sep-12 Release date: 03-Oct-12

Protein chain

P04818  (TYSY_HUMAN) -  Thymidylate synthase from Homo sapiens

Seq: 313 a.a.

Struc: 263 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.45 - thymidylate synthase.
• Pathway: Folate Coenzymes
• Reaction: dUMP + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate = 7,8-dihydrofolate + dTMP

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1042/BSR20140137

Biosci Rep 34:e00168 (2014)

PubMed id: 25423174

Analysis of mRNA recognition by human thymidylate synthase.

N.D.Brunn, S.M.Dibrov, M.B.Kao, M.Ghassemian, T.Hermann.

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.