Computational study of the mechanism of half-reactions in class 1A dihydroorotate dehydrogenase from Trypanosoma cruzi

Silva, Natália de Farias; Lameira, Jerônimo; Alves, Cláudio Nahum; Martí, Sérgio

doi:10.1039/c3cp52692e

Cited by 7 publications

(1 citation statement)

References 51 publications

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“…A ping-pong Bi-Bi mechanism is followed by TcDHODH, where dihydroorotate binds first to the enzyme followed by fumarate, a mechanism revealed by the use of barbiturate (BA) a known dead end inhibitor of DHODH. In another study reaction mechanism of TcDHODH was studied by employing hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) Molecular Dynamics (MD) simulations [ 41 ]. FMN was identified as a prosthetic group of TcDHODH by TLC analysis [ 31 ].…”

Section: Enzymes Of the Pyrimidine Pathway Of Trypanosomatidsmentioning

confidence: 99%

Fresh insights into the pyrimidine metabolism in the trypanosomatids

Tiwari

Dubey

2018

Parasites Vectors

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The trypanosomatid parasites continue their killing spree resulting in significant annual mortality due to the lack of effective treatments and the prominence of these diseases in poorer countries. These dimorphic parasites thrive unchecked in the host system, outsmarting the immune mechanisms. An understanding of biology of these parasitic forms will help in the management and elimination of these fatal diseases. Investigation of various metabolic pathways in these parasites has shed light in the understanding of the unique biology of the trypansomatids. An understanding of these pathways have helped in tracing the soft targets in the metabolic pathways, which could be used as effective drug targets which would further impact the therupeutic implications. Pyrimidine pathway is a vital metabolic pathway which yields in the formation of pyrimidines, which are then integrated in nucleic acids (DNA and RNA) in sugars (UDP sugars) and lipids (CDP lipids). A wealth of data and information has been generated in the past decades by in-depth analyses of pyrimidine pathway in the trypanosomatid parasites, which can aid in the identification of anomalies between the parasitic and host counterpart which could be further harnessed to develop therapeutic interventions for the treatment of parasitic diseases. This review presents an updated and comprehensive detailing of the pyrimidine metabolism in the trypansomatids, their uniqueness and their distinctions, and its possible outcomes that would aid in the eradication of these parasitic diseases.

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Section: Enzymes Of the Pyrimidine Pathway Of Trypanosomatidsmentioning

confidence: 99%

Fresh insights into the pyrimidine metabolism in the trypanosomatids

Tiwari

Dubey

2018

Parasites Vectors

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Antioxidant Activity of an Industrial Cupuassu Seed By‐product: Molecular Modeling of Phenolic Compounds

et al. 2018

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To better understand the biological properties of cupuassu seed residue resulting from fruit industrial processing, its antioxidant activity was determined by both the 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) assays. Molecular modeling was used to correlate the antiradical power of eleven known cupuassu phenolic compounds with their structures. The extract antioxidant activity by both methods was very high compared with those of similar residues. The properties of the highest occupied and lowest unoccupied molecular orbitals indicate that the most energetically stable compounds possess the highest antioxidant activity. This was confirmed through the molecular electrostatic potential map by the nucleophilic surfaces on the oxygen atoms of carbonyl and hydroxyl groups.

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