4GTC

T. Maritima FDTS (E144R mutant) plus FAD

4GTC の概要

• エントリーDOI: 10.2210/pdb4gtc/pdb
• 分子名称: Thymidylate synthase thyX, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: flavin-dependent thymidylate synthase, tm0449, transferase
• 由来する生物種: Thermotoga maritima
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 113269.24

構造登録者

Mathews, I.I.,Lesley, S.A.,Kohen, A.,Prabhakar, A. (登録日: 2012-08-28, 公開日: 2012-10-17, 最終更新日: 2023-09-13)

主引用文献

Koehn, E.M.,Perissinotti, L.L.,Moghram, S.,Prabhakar, A.,Lesley, S.A.,Mathews, I.I.,Kohen, A.
Folate binding site of flavin-dependent thymidylate synthase.
Proc.Natl.Acad.Sci.USA, 109:15722-15727, 2012

PubMed Abstract: The DNA nucleotide thymidylate is synthesized by the enzyme thymidylate synthase, which catalyzes the reductive methylation of deoxyuridylate using the cofactor methylene-tetrahydrofolate (CH(2)H(4)folate). Most organisms, including humans, rely on the thyA- or TYMS-encoded classic thymidylate synthase, whereas, certain microorganisms, including all Rickettsia and other pathogens, use an alternative thyX-encoded flavin-dependent thymidylate synthase (FDTS). Although several crystal structures of FDTSs have been reported, the absence of a structure with folates limits understanding of the molecular mechanism and the scope of drug design for these enzymes. Here we present X-ray crystal structures of FDTS with several folate derivatives, which together with mutagenesis, kinetic analysis, and computer modeling shed light on the cofactor binding and function. The unique structural data will likely facilitate further elucidation of FDTSs' mechanism and the design of structure-based inhibitors as potential leads to new antimicrobial drugs.

PubMed: 23019356
DOI: 10.1073/pnas.1206077109

実験手法

X-RAY DIFFRACTION (1.97 Å)