PMID:10386884
| Citation |
Shen, BW, Dyer, DH, Huang, JY, D'Ari, L, Rabinowitz, J and Stoddard, BL (1999) The crystal structure of a bacterial, bifunctional 5,10 methylene-tetrahydrofolate dehydrogenase/cyclohydrolase. Protein Sci. 8:1342-9 |
|---|---|
| Abstract |
The structure of a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/cyclohydrolase from Escherichia coli has been determined at 2.5 A resolution in the absence of bound substrates and compared to the NADP-bound structure of the homologous enzyme domains from a trifunctional human synthetase enzyme. Superposition of these structures allows the identification of a highly conserved cluster of basic residues that are appropriately positioned to serve as a binding site for the poly-gamma-glutamyl tail of the tetrahydrofolate substrate. Modeling studies and molecular dynamic simulations of bound methylene-tetrahydrofolate and NADP shows that this binding site would allow interaction of the nicotinamide and pterin rings in the dehydrogenase active site. Comparison of these enzymes also indicates differences between their active sites that might allow the development of inhibitors specific to the bacterial target. |
| Links |
PubMed PMC2144347 Online version:10.1110/ps.8.6.1342 |
| Keywords |
Aminohydrolases/chemistry; Aminohydrolases/metabolism; Binding Sites; Crystallography, X-Ray; Dimerization; Escherichia coli/enzymology; Humans; Methylenetetrahydrofolate Dehydrogenase (NADP)/chemistry; Methylenetetrahydrofolate Dehydrogenase (NADP)/metabolism; Models, Molecular; Multienzyme Complexes/chemistry; Multienzyme Complexes/metabolism; Protein Conformation; Tetrahydrofolates/metabolism |
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