1. HARDY, L.W., FINERMOORE, J.S., MONTFORT, W.R., JONES, M.O., SANTI, D.V.
AND STROUD, R.M.
Atomic structure of thymidylate synthase - Target for rational drug design.
SCIENCE 235 448-455 (1987).
2. KANEDA, S., NALBANTOGLU, J., TAKEISHI, K., SHIMIZU, K., GOTOH, O, SENO,
T. AND AYUSAWA, D.
Structural and functional analysis of the human thymidylate synthase gene.
J.BIOL.CHEM. 265(33) 20277-20284 (1990).
Thymidylate synthase catalyses the conversion of deoxypuridine monophosphate
(dUMP) and 5,10-methylenetetrahydrofolate to oxythymidine monophosphate
(dTMP) and dihydrofolate. This provides the sole de novo pathway for
production of dTMP and is the only enzyme in folate metabolism in which the
5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer .
The enzyme is essential for regulating the balanced supply of the 4 DNA
precursors in normal DNA replication: defects in the enzyme activity
affecting the regulation process cause various biological and genetic
abnormalities, such as thymineless death . The enzyme exists as a homo-
dimer, and is also found as a bifunctional enzyme in protozoa, containing
dihydrofolate reductase activity .
THYMDSNTHASE is a 5-element fingerprint that provides a signature for
thymidylate synthases. The fingerprint was derived from an initial
alignment of 9 sequences: the motifs surround the active site, motif 4
including the region encoded by PROSITE pattern THYMIDYLATE_SYNTHASE
(PS00091), which contains the catalytically important Cys residue. Two
iterations on OWL21.1 were required to reach convergence, at which point
a true set comprising 30 sequences was identified. A single partial match
was also found, TYSY_LACLA, a thymidylate synthase fragment.
An update on SPTR37_9f identified a true set of 47 sequences, and 4