1B02

CRYSTAL STRUCTURE OF THYMIDYLATE SYNTHASE A FROM BACILLUS SUBTILIS

Summary for 1B02

• Entry DOI: 10.2210/pdb1b02/pdb
• Descriptor: PROTEIN (THYMIDYLATE SYNTHASE), 5-FLUORO-2'-DEOXYURIDINE-5'-MONOPHOSPHATE, 5-METHYL-5,6,7,8-TETRAHYDROFOLIC ACID, ... (4 entities in total)
• Functional Keywords: transferase, methyltransferase
• Biological source: Bacillus subtilis
• Total number of polymer chains: 1
• Total formula weight: 33633.80

Authors

Fox, K.M.,Maley, F.,Garibian, A.,Changchien, L.,Vanroey, P. (deposition date: 1998-11-16, release date: 1999-03-29, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)