EC Number   |
General Information |
Reference |
|---|
    1.5.1.3 | evolution |
alignment analysis shows several substitutions between Schistosoma mansoni and human DHFR at both the folate- and NADP+-binding sites. The folate-binding site exhibits two differences at three residues (human DHFR numbering): E30D and N64F. The NADP+-binding site exhibits six substitutions at 11 residues: D21G,K54R, K55V, R76S, E77T and S118Y |
741552 |
| 1.5.1.3 | evolution |
dihydrofolate reductase (DHFR) and thymidylate synthase (TS) have undergone a fusion event generating a single polypeptide but conserving the two functions in trypanosomatids |
742057 |
| 1.5.1.3 | evolution |
identification of a second functional dihydrofolate reductase enzyme in humans, DHFRL1. RNA-mediated DHFR duplication events occur across the mammal tree. Dihydrofolate reductase activity is also a feature of the mitochondria in both rat and mouse but this is not due to a second enzyme. Humans have evolved the need for two separate enzymes, while laboratory rats and mice have just one. RNA-mediated DHFR duplicates in brown rat and mouse are likely to be processed pseudogenes |
742518 |
| 1.5.1.3 | evolution |
PTR1 is a NADPH-dependent enzyme belonging to the short-chain dehydrogenase/reductase (SDR) family |
765513 |
| 1.5.1.3 | evolution |
PTR1 is a short-chain dehydrogenase reductase family member. The trypanosomatid PTR1s are structurally very similar, sequence comparisons |
765417 |
| 1.5.1.3 | evolution |
PTR2 is a short-chain dehydrogenase reductase family member. In Trypanosoma cruzi, TcPTR1 and TcPTR2 are isoforms that show very high sequence homology but also display varied enzymatic activity. TcPTR1 in comparison to TcPTR2 shows higher activity with biopterin and folate than with H2F or H2B |
765417 |
| 1.5.1.3 | evolution |
replacement of Asp27 in Escherichia coli DHFR by Glu27 in Moritella DHFR may be an adaptation for cold that fortuitously also enhances activity under pressure. The extra carbon of a glutamate increases flexibility of the Thr113-Res27 hydrogen bond while pressure increases the hydrogen bond strength and correlation of sheet F with helix B |
765363 |
| 1.5.1.3 | evolution |
the enzyme belong to the short-chain dehydrogenase/reductase (SDR) family of enzymes. Despite the overall low sequence identity among members of the SDR family (about 15-30%), a central catalytic YX3K motif is highly conserved, as is an N-terminal glycine motif (TGX3GXG), involved in cofactor binding and recognition. The pteridine reductases in the SDR family have an arginine in place of the glycine at position 6 in this motif (TGX3RXG) |
765008 |
| 1.5.1.3 | evolution |
Tyr103 of Moritella yayanosii DHFR may be an adaptation for high pressure since Cys103 in helix F of Moritella profunda DHFR forms an intra-helix hydrogen bond with Ile99 while Tyr103 in helix F of MyDHFR forms a hydrogen bond with Leu78 in helix E. Tyr 103 may be an adaptation for preventing distortion of the adenosine binding domain at higher pressures that may only be advantageous for cold-adapted DHFRs |
765363 |
| 1.5.1.3 | malfunction |
enzyme knockdown results in the abnormal developments of zebrafish embryos in the early stages. Obvious malformations in heart and outflow tract are also observed in knockdown embryos. Enzyme knockdown causes reduced cell proliferation and increased apoptosis |
723815 |
