4LRR

Ternary complex between E. coli thymidylate synthase, dUMP, and F9

Summary for 4LRR

• Entry DOI: 10.2210/pdb4lrr/pdb
• Related: 4LRP
• Descriptor: Thymidylate synthase, SULFATE ION, 2-oxo-2H-naphtho[1,8-bc]furan-6-yl 4-nitrobenzoate, ... (5 entities in total)
• Functional Keywords: thymidine monophosphate synthesis, n-terminal acetylated methionine, beta-mercaptoethanol modified cysteine, transferase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm (By similarity): P0A886
• Total number of polymer chains: 1
• Total formula weight: 31999.74

Authors

Mangani, S.,Pozzi, C.,Ferrari, S.,Costi, M.P. (deposition date: 2013-07-20, release date: 2013-11-06, Last modification date: 2013-12-11)

Primary citation

Ferrari, S.,Calo, S.,Leone, R.,Luciani, R.,Costantino, L.,Sammak, S.,Di Pisa, F.,Pozzi, C.,Mangani, S.,Costi, M.P.
2'-Deoxyuridine 5'-Monophosphate Substrate Displacement in Thymidylate Synthase through 6-Hydroxy-2H-naphtho[1,8-bc]furan-2-one Derivatives.
J.Med.Chem., 56:9356-9360, 2013

PubMed Abstract: 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 toward the dimeric protein interface, thus providing new opportunities for further design of specific inhibitors of microbial pathogens.

PubMed: 24147825
DOI: 10.1021/jm4014086

Experimental method

X-RAY DIFFRACTION (2.41 Å)