Structural modeling identifies Plasmodium vivax 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) as a plausible new antimalarial drug target

Kadian, Kavita; Vijay, Sonam; Gupta, Yash; Rawal, Ritu; Singh, Jagbir; Anvikar, Anup; Pande, Veena; Sharma, Arun Dev

doi:10.1016/j.parint.2018.03.001

Cited by 3 publications

(1 citation statement)

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“…IspE is a cytoplasmic kinase of the MEP pathway that is involved in the biosynthesis of the isoprenoids used by many Gram-negative bacteria (including E. coli, Salmonella enterica, P. aeruginosa and H. influenzae ), as well as Gram-positive bacteria such as Clostridium difficile and Bacillus subtilis , M. tuberculosis , and even few apicoplast protozoa such as Plasmodium falciparum 66 . Because isoprenoids are involved in a wide variety of vital biological functions, the seven enzymes without close human homologs that participate in their metabolism (Dxs, IspC, IspD, IspE, IspF, IspG, IspH) are favorable candidate drug targets and several inhibitors have been already reported 67 , mainly as antimalarial targets 68 , 69 . In Gram-negative bacteria, compounds from the isoxazol-5(4 H)-one series have been evaluated (e.g.…”

Section: Resultsmentioning

confidence: 99%

An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets

Ramos

Porto

Lanzarotti

et al. 2018

Sci Rep

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Klebsiella pneumoniae (Kp) is a globally disseminated opportunistic pathogen that can cause life-threatening infections. It has been found as the culprit of many infection outbreaks in hospital environments, being particularly aggressive towards newborns and adults under intensive care. Many Kp strains produce extended-spectrum β-lactamases, enzymes that promote resistance against antibiotics used to fight these infections. The presence of other resistance determinants leading to multidrug-resistance also limit therapeutic options, and the use of ‘last-resort’ drugs, such as polymyxins, is not uncommon. The global emergence and spread of resistant strains underline the need for novel antimicrobials against Kp and related bacterial pathogens. To tackle this great challenge, we generated multiple layers of ‘omics’ data related to Kp and prioritized proteins that could serve as attractive targets for antimicrobial development. Genomics, transcriptomics, structuromic and metabolic information were integrated in order to prioritize candidate targets, and this data compendium is freely available as a web server. Twenty-nine proteins with desirable characteristics from a drug development perspective were shortlisted, which participate in important processes such as lipid synthesis, cofactor production, and core metabolism. Collectively, our results point towards novel targets for the control of Kp and related bacterial pathogens.

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Section: Resultsmentioning

confidence: 99%