1kq4

Protein Summary

Gene TM0449 from Thermotoga maritima encodes a flavin-dependent Thymidylate Synthase Thy1 (ThyX)  (EC.2.1.1.148; 5,10-methylenetetrahydrofolate,FADH2:dUMP C-methyltransferase) that belongs to Pfam02511 and are similar to proteins from COG1351. Thy1 (ThyX) enzymes are mainly limited to microbial and viral genomes that lack ThyA and are an important drug target as they occur in several pathogens like e.g.: Helicobacter pylori, Chlamydia trachomatis or Mycobacterium tuberculosis but are absent in humans (PubMed:12029065, 16730023). 

When the structure of Thy1 from Thermotoga maritima solved by JCSG was published in 2002, it was correctly proposed that Thy1 is capable of both methyl transfer and reduction of substrate or a cofactor (PubMed:12211025). The flavin-dependent thymidylate synthesis was described in details in a series of papers (PubMed:12029065, 16730023, 15123820, 15591067, 16707489). Despite enormous amount of research data gathered since the first reports about Thy1 function (PubMed:12029065) and structure (PubMed:12211025) new interesting properties of this enzymes, like RNA-binding (PubMed:16176183) are being discovered.
Thy1 (TM0449) from Thermotoga maritima is a tetramer composed of identical 220-residue subunits with a unique ?+? fold (SCOP fold id: 69795) where each monomer consist of: antiparallel 5-stranded ?-sheet (order 12354), a long ?-helix, and six ?-helices on one side of the sheet (Figure 1) (PubMed:12211025). The interface between subunits of Thy1 tetramer is formed by a partial stacking of the ?-sheets and two long helices, where a large active site pocket with four channels running along the molecular interfaces is formed (PubMed:12211025).

Ligand Summary

References