1o5z

Protein Summary

The TM0166 gene from Thermotoga maritima encodes a folylpolyglutamate synthase (FPGS) (PF02825, COG0285), an ATP-dependent enzyme that catalyzes the addition of a polyglutamate tail to folate and folate derivatives thereby playing a key role in the retention of intracellular folate. FPGS has been employed in the production of anticancer drugs with increased cytotoxicity [Ref] and is also considered an attractive target for anti-microbial therapy [Ref]. change.[Ref]

The structure reveals a two-domain organization and is highly similar (main-chain rmsd 1.7 Å over 358 residues with a sequence identity of 33%) with the FPGS from Lactobacillus casei (PDB id: 2fgs [Ref]). The active site of TM0116, located in a large interdomain cleft adjacent to an ATP-binding P-loop motif (GTNGKGS, TM0116 residues 46-51), contains an unidentified ligand that by comparison with 2fgs and 1w7k is likely to be a mimetic for ATP. A second unidentified ligand, located along a C-terminal cleft, is likely to indicate the site of folate binding. See [Ref] for more details on the structure and active site.

Ligand Summary

References