1B02

CRYSTAL STRUCTURE OF THYMIDYLATE SYNTHASE A FROM BACILLUS SUBTILIS

1B02 の概要

• エントリーDOI: 10.2210/pdb1b02/pdb
• 分子名称: PROTEIN (THYMIDYLATE SYNTHASE), 5-FLUORO-2'-DEOXYURIDINE-5'-MONOPHOSPHATE, 5-METHYL-5,6,7,8-TETRAHYDROFOLIC ACID, ... (4 entities in total)
• 機能のキーワード: transferase, methyltransferase
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33633.80

構造登録者

Fox, K.M.,Maley, F.,Garibian, A.,Changchien, L.,Vanroey, P. (登録日: 1998-11-16, 公開日: 1999-03-29, 最終更新日: 2024-11-13)

主引用文献

Fox, K.M.,Maley, F.,Garibian, A.,Changchien, L.M.,Van Roey, P.
Crystal structure of thymidylate synthase A from Bacillus subtilis.
Protein Sci., 8:538-544, 1999

PubMed Abstract: Thymidylate synthase (TS) converts dUMP to dTMP by reductive methylation, where 5,10-methylenetetrahydrofolate is the source of both the methylene group and reducing equivalents. The mechanism of this reaction has been extensively studied, mainly using the enzyme from Escherichia coli. Bacillus subtilis contains two genes for TSs, ThyA and ThyB. The ThyB enzyme is very similar to other bacterial TSs, but the ThyA enzyme is quite different, both in sequence and activity. In ThyA TS, the active site histidine is replaced by valine. In addition, the B. subtilis enzyme has a 2.4-fold greater k(cat) than the E. coli enzyme. The structure of B. subtilis thymidylate synthase in a ternary complex with 5-fluoro-dUMP and 5,10-methylenetetrahydrofolate has been determined to 2.5 A resolution. Overall, the structure of B. subtilis TS (ThyA) is similar to that of the E. coli enzyme. However, there are significant differences in the structures of two loops, the dimer interface and the details of the active site. The effects of the replacement of histidine by valine and a serine to glutamine substitution in the active site area, and the addition of a loop over the carboxy terminus may account for the differences in k(cat) found between the two enzymes.

PubMed: 10091656

実験手法

X-RAY DIFFRACTION (2.5 Å)