4O1M

Toxoplasma gondii Enoyl acyl carrier protein reductase

Summary for 4O1M

• Entry DOI: 10.2210/pdb4o1m/pdb
• Related: 2O2S 2O2Y 2O50 2PTG 3NJ8
• Descriptor: Enoyl-acyl carrier reductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase, enoyl acyl carrier protein reductase
• Biological source: Toxoplasma gondii
• Total number of polymer chains: 6
• Total formula weight: 204329.88

Authors

Muench, S.P.,Wilkinson, C.,Prigge, S.T.,Rice, D.W. (deposition date: 2013-12-16, release date: 2014-02-05, Last modification date: 2024-04-03)

Primary citation

Wilkinson, C.,Mcphillie, M.J.,Zhou, Y.,Woods, S.,Afanador, G.A.,Rawson, S.,Khaliq, F.,Prigge, S.T.,Roberts, C.W.,Rice, D.W.,Mcleod, R.,Fishwick, C.W.,Muench, S.P.
The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target
Bioorg.Med.Chem.Lett., 24:911-916, 2014

PubMed Abstract: The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD(+) bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD(+) and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against Toxoplasma gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1 μM. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there may be significant off target effects for this family of inhibitors.

PubMed: 24398298
DOI: 10.1016/j.bmcl.2013.12.066

Experimental method

X-RAY DIFFRACTION (2 Å)