Structural highlights
4lrr is a 1 chain structure with sequence from Escherichia coli O157:H7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.41Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TYSY_ECO57 Provides the sole de novo source of dTMP for DNA biosynthesis (By similarity).
Publication Abstract from PubMed
Thymidylate synthase (TS) is a target for antifolate-based chemotherapies of microbial and human diseases. Here, ligand-based, synthetic and X-ray crystallography studies led to the discovery of 6-(3-cyanobenzoyloxy)-2-oxo-2H-naphto[1,8-bc]furan, a novel inhibitor with a Ki of 310 nM against Pneumocystis carinii TS. The X-ray ternary complex with Escherichia coli TS revealed, for the first time, displacement of the substrate towards the dimeric protein interface, thus providing new opportunities for further design of specific inhibitors of microbial pathogens.
2'-deoxyuridine-5'-monophosphate substrate displacement in thymidylate synthase through 6-hydroxy-2H-naphtho[1,8-bc]furan-2-one derivatives.,Ferrari S, Calo S, Leone R, Luciani R, Costantino L, Sammak S, Di Pisa F, Pozzi C, Mangani S, Costi MP J Med Chem. 2013 Oct 22. PMID:24147825[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ferrari S, Calo S, Leone R, Luciani R, Costantino L, Sammak S, Di Pisa F, Pozzi C, Mangani S, Costi MP. 2'-deoxyuridine-5'-monophosphate substrate displacement in thymidylate synthase through 6-hydroxy-2H-naphtho[1,8-bc]furan-2-one derivatives. J Med Chem. 2013 Oct 22. PMID:24147825 doi:http://dx.doi.org/10.1021/jm4014086
