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PDBsum entry 1vze
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Methyltransferase
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PDB id
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1vze
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References listed in PDB file
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Key reference
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Title
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The separate effects of e60q in lactobacillus casei thymidylate synthase delineate between mechanisms for formation of intermediates in catalysis.
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Authors
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D.L.Birdsall,
W.Huang,
D.V.Santi,
R.M.Stroud,
J.Finer-Moore.
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Ref.
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Protein Eng, 1998,
11,
171-183.
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PubMed id
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Abstract
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X-Ray crystal structures of Lactobacillus casei thymidylate synthase (TS) mutant
complexes of E60D with dUMP, and E60Q with dUMP or FdUMP, as well as ternary
complexes with folate analog inhibitor CB3717, are described. The structures we
report address the decrease in rate of formation of ternary complexes in the E60
mutants. Structures of ternary complexes of L.casei TS mimic ligand-bound TS
just prior to covalent bond formation between ligands and protein. Ternary
complex structures of L.casei TS E60Q show the ligands are not optimally aligned
for making the necessary covalent bonds. Since CB3717 is an analog of the open,
activated form of the cofactor, these structures suggest that the slow rate of
ternary complex formation in E60 mutants is at least partly the result of
impaired alignment of ligands in the active site after binding and activation of
the cofactor. Binary complexes of TS E60Q and TS E60D with substrate (dUMP) show
no change in dUMP position or occupancy. These results are consistent with the
fact that Kd(dUMP) and Km(dUMP) are almost the same, and the rates of
folate-independent debromination of 5-bromo-dUMP are even higher than for wild
type TS.
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Secondary reference #1
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Title
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Refined structures of substrate-Bound and phosphate-Bound thymidylate synthase from lactobacillus casei.
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Authors
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J.Finer-Moore,
E.B.Fauman,
P.G.Foster,
K.M.Perry,
D.V.Santi,
R.M.Stroud.
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Ref.
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J Mol Biol, 1993,
232,
1101-1116.
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PubMed id
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