4LRR

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

PDB DOI: https://doi.org/10.2210/pdb4LRR/pdb

Classification: TRANSFERASE
Organism(s): Escherichia coli O157:H7
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2013-07-20 Released: 2013-11-06
Deposition Author(s): Mangani, S., Pozzi, C., Ferrari, S., Costi, M.P.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.41 Å
R-Value Free: 0.230
R-Value Work: 0.170
R-Value Observed: 0.173

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

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, M.P.

(2013) J Med Chem 56: 9356-9360

PubMed: 24147825 Search on PubMed
DOI: https://doi.org/10.1021/jm4014086
Primary Citation of Related Structures:
4LRR

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.

Organizational Affiliation

Department of Life Sciences, University of Modena and Reggio Emilia , Via Campi 183, 41125 Modena, Italy.

Macromolecule Content

Total Structure Weight: 32 kDa
Atom Count: 2,395
Modelled Residue Count: 265
Deposited Residue Count: 265
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Thymidylate synthase	A	265	Escherichia coli O157:H7	Mutation(s): 1 Gene Names: thyA EC: 2.1.1.45
UniProt
Find proteins for P0A886 (Escherichia coli O157:H7) Explore P0A886 Go to UniProtKB: P0A886
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P0A886
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
CF9 Query on CF9 Download Ideal Coordinates CCD File SDF format, chain J [auth A] MOL2 format, chain J [auth A]	J [auth A]	2-oxo-2H-naphtho[1,8-bc]furan-6-yl 4-nitrobenzoate C₁₈ H₉ N O₆ JZRRRFGHBXIXDI-UHFFFAOYSA-N		Interactions Focus chain J [auth A] Interactions & Density Focus chain J [auth A]
UMP Query on UMP Download Ideal Coordinates CCD File SDF format, chain K [auth A] MOL2 format, chain K [auth A]	K [auth A]	2'-DEOXYURIDINE 5'-MONOPHOSPHATE C₉ H₁₃ N₂ O₈ P JSRLJPSBLDHEIO-SHYZEUOFSA-N		Interactions Focus chain K [auth A] Interactions & Density Focus chain K [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain B [auth A] SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] MOL2 format, chain B [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A]	B [auth A] C [auth A] D [auth A] E [auth A] F [auth A] B [auth A], C [auth A], D [auth A], E [auth A], F [auth A], G [auth A], H [auth A], I [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain B [auth A] Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Interactions & Density Focus chain B [auth A] Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A]