Structure of Mtb 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) complexed with CTP

Reddy, M. Siva Pratap; Bruning, J.B.; Thurman, C.; Ioerger, Thomas R.; Sacchettini, J.C.

doi:10.2210/pdb3q7u/pdb

2011

DOI: 10.2210/pdb3q7u/pdb

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Structure of Mtb 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) complexed with CTP

M. Siva Pratap Reddy¹,

J.B. Bruning²,

C. Thurman³

et al.

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2014

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Development of Inhibitors of the 2C-Methyl-d-erythritol 4-Phosphate (MEP) Pathway Enzymes as Potential Anti-Infective Agents

Masini

Hirsch²

2014

J. Med. Chem.

114

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Important pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum, the causative agents of tuberculosis and malaria, respectively, and plants, utilize the 2C-methyl-D-erythritol 4-phosphate (MEP, 5) pathway for the biosynthesis of isopentenyl diphosphate (1) and dimethylallyl diphosphate (2), the universal precursors of isoprenoids, while humans exclusively utilize the alternative mevalonate pathway for the synthesis of 1 and 2. This distinct distribution, together with the fact that the MEP pathway is essential in numerous organisms, makes the enzymes of the MEP pathway attractive drug targets for the development of anti-infective agents and herbicides. Herein, we review the inhibitors reported over the past 2 years, in the context of the most important older developments and with a particular focus on the results obtained against enzymes of pathogenic organisms. We will also discuss new discoveries in terms of structural and mechanistic features, which can help to guide a rational development of inhibitors.

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Development of Inhibitors of the 2C-Methyl-d-erythritol 4-Phosphate (MEP) Pathway Enzymes as Potential Anti-Infective Agents

Masini

Hirsch²

2014

J. Med. Chem.

114

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Structure of Mtb 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) complexed with CTP

Cited by 1 publication

References 0 publications

Development of Inhibitors of the 2C-Methyl-d-erythritol 4-Phosphate (MEP) Pathway Enzymes as Potential Anti-Infective Agents

Development of Inhibitors of the 2C-Methyl-d-erythritol 4-Phosphate (MEP) Pathway Enzymes as Potential Anti-Infective Agents

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