4ELH

Structure-activity relationship guides enantiomeric preference among potent inhibitors of B. anthracis dihydrofolate reductase

Summary for 4ELH

• Entry DOI: 10.2210/pdb4elh/pdb
• Related: 3ELB 3ELE 3ELF 3FL8 3FL9 4ELG
• Descriptor: Dihydrofolate reductase, CALCIUM ION, (2E)-3-{5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl}-1-[(1R)-1-(2-methylprop-1-en-1-yl)phthalazin-2(1H)-y l]prop-2-en-1-one, ... (6 entities in total)
• Functional Keywords: dihydrofolate reductase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Bacillus anthracis (anthrax,anthrax bacterium)
• Total number of polymer chains: 8
• Total formula weight: 162015.06

Authors

Bourne, C.R.,Barrow, W.W. (deposition date: 2012-04-10, release date: 2013-02-13, Last modification date: 2023-09-13)

Primary citation

Bourne, C.R.,Wakeham, N.,Nammalwar, B.,Tseitin, V.,Bourne, P.C.,Barrow, E.W.,Mylvaganam, S.,Ramnarayan, K.,Bunce, R.A.,Berlin, K.D.,Barrow, W.W.
Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase.
Biochim.Biophys.Acta, 1834:46-52, 2013

PubMed Abstract: Bacterial resistance to antibiotic therapies is increasing and new treatment options are badly needed. There is an overlap between these resistant bacteria and organisms classified as likely bioterror weapons. For example, Bacillus anthracis is innately resistant to the anti-folate trimethoprim due to sequence changes found in the dihydrofolate reductase enzyme. Development of new inhibitors provides an opportunity to enhance the current arsenal of anti-folate antibiotics while also expanding the coverage of the anti-folate class.

PubMed: 22999981
DOI: 10.1016/j.bbapap.2012.09.001

Experimental method

X-RAY DIFFRACTION (2.103 Å)