3E0B: Bacillus Anthracis Dihydrofolate Reductase Complexed With Nadph And 2, 4-diamino-5-(3-(2,5-dimethoxyphenyl)prop-1-ynyl)-6-ethylpyrimidine (ucp120b)

Bacillus anthracis, the causative agent of anthrax, poses a significant biodefense danger. Serious limitations in approved therapeutics and the generation of resistance have produced a compelling need for new therapeutic agents against this organism. Bacillus anthracis is known to be insensitive to the clinically used antifolate, trimethoprim, because of a lack of potency against the dihydrofolate reductase enzyme. Herein, we describe a novel lead series of B. anthracis dihydrofolate reductase inhibitors characterized by an extended trimethoprim-like scaffold. The best lead compound adds only 22 Da to the molecular weight and is 82-fold more potent than trimethoprim. An X-ray crystal structure of this lead compound bound to B. anthracis dihydrofolate reductase in the presence of NADPH was determined to 2.25 A resolution. The structure reveals several features that can be exploited for further development of this lead series.
PDB ID: 3E0BDownload
MMDB ID: 68140
PDB Deposition Date: 2008/7/31
Updated in MMDB: 2008/12
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Similar Structures:
Biological Unit for 3E0B: monomeric; determined by author and by software (PISA)
Molecular Components in 3E0B
Label Count Molecule
Protein (1 molecule)
Dihydrofolate Reductase
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB