Dataset Information

Inhibitory Activity and Docking Analysis of Antimalarial Agents from Stemona sp. toward Ferredoxin-NADP+ Reductase from Malaria Parasites.

ABSTRACT: Ferredoxin-NADP+ reductases (FNRs, EC 1.18.1.2) were found in the plastids of Plasmodium and have been considered as a target for the development of new antimalarial agents. Croomine, epi-croomine, tuberostemonine, javastemonine A, and isoprotostemonine are isolated alkaloids from the roots of Stemona sp. and their inhibitory effect on FNRs from Plasmodium falciparum (PfFNR) was investigated. Croomine showed the highest level of inhibition (33.9%) of electron transfer from PfFNR to PfFd, while tuberstemonine displayed the highest level of inhibition (55.4%) of diaphorase activity of PfFNR. Docking analysis represented that croomine is located at the middle position of PfFNR and PfFd. Croomine from S. tuberosa appeared to have potential as an antimalarial agent.

SUBMITTER: Pudjiastuti P

PROVIDER: S-EPMC6129339 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Inhibitory Activity and Docking Analysis of Antimalarial Agents from Stemona sp. toward Ferredoxin-NADP+ Reductase from Malaria Parasites.

Pudjiastuti Pratiwi P Puspaningsih Ni Nyoman T NNT Siswanto Imam I Fanani Much Z MZ Ariga Yoko K YK Hase Toshiharu T Sarker Satyajit D SD Nahar Lutfun L

Journal of parasitology research 20180826

Ferredoxin-NADP+ reductases (FNRs, EC 1.18.1.2) were found in the plastids of Plasmodium and have been considered as a target for the development of new antimalarial agents. Croomine, epi-croomine, tuberostemonine, javastemonine A, and isoprotostemonine are isolated alkaloids from the roots of Stemona sp. and their inhibitory effect on FNRs from Plasmodium falciparum (PfFNR) was investigated. Croomine showed the highest level of inhibition (33.9%) of electr ...[more]

PMID: 30225138

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Project description:Ferredoxin: NADP+ reductase (FNR) is an FAD-containing enzyme best known for catalysing the transfer of electrons from ferredoxin (Fd) to NADP+ to make NADPH during photosynthesis. It is also the prototype for a broad enzyme superfamily, including the NADPH oxidases (NOXs) that all catalyse similar FAD-enabled electron transfers between NAD(P)H and one-electron carriers. Here, we define further mechanistic details of the NAD(P)H ? FAD hydride-transfer step of the reaction based on spectroscopic studies and high-resolution (~ 1.5 Å) crystallographic views of the nicotinamide-flavin interaction in crystals of corn root FNR Tyr316Ser and Tyr316Ala variants soaked with either nicotinamide, NADP+ , or NADPH. The spectra obtained from FNR crystal complexes match those seen in solution and the complexes reveal active site packing interactions and patterns of covalent distortion of the FAD that imply significant active site compression that would favour catalysis. Furthermore, anisotropic B-factors show that the mobility of the C4 atom of the nicotinamide in the FNR:NADP+ complex has a directionality matching that expected for boat-like excursions of the nicotinamide ring thought to enhance hydride transfer. Arguments are made for the relevance of this binding mode to catalysis, and specific consideration is given to how the results extrapolate to provide insight to structure-function relations for the membrane-bound NOX enzymes for which little structural information has been available. DATABASES:Structural data are available in the PDB database under the accession numbers 3LO8 (wild-type), 5VW4 [Y316S:nicotinamide (P32 21)], 5VW9 [Y316S:nicotinamide (P31 21)], 5VW3 [Y316S:NADP+ (P32 21)], 5VW8 [Y316S:NADP+ (P31 21)], 5VW2 [Y316S:NADPH (P32 21)], 5VW5 [Y316A:nicotinamide (P32 21)], 5VW6 [Y316A:NADP+ (P32 21)], 5VW7 [Y316A:NADPH (P32 21)], 5VWA [Y316F (P32 21)], and 5VWB [Y316F:NADP+ (P31 21)]. Enzyme Commission number: ferredoxin:NADP+ reductase - E C1.18.1.2.

Dataset Information

Inhibitory Activity and Docking Analysis of Antimalarial Agents from Stemona sp. toward Ferredoxin-NADP+ Reductase from Malaria Parasites.

Publications

Inhibitory Activity and Docking Analysis of Antimalarial Agents from <i>Stemona</i> sp. toward Ferredoxin-NADP+ Reductase from Malaria Parasites.

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