Dataset Information

Structural insight into the binding of C60-derivatives with enoyl-pyruvate transferase from Helicobacter pylori.

ABSTRACT: Helicobacter pylori (H. pylori) is a human pathogen associated with acute gastritis and peptic ulcer. The MurA enzyme is an important drug target for the identification of ligands with improved efficacy and acceptable pharmaco-kinetic properties. We developed a homology model of H. Pylori MurA followed by refinement and molecular dynamics (MD) simulations. A total of 16 C60-derivatives were docked and its docking score were compared. Some of the known inhibitors were also similarly characterized and compared. Results show that five out of the sixteen C60-derivatives have good binding score. The MMPBSA analysis for the top five C60- derivatives shows good binding energy. This study reports the interaction patterns of selected C60 derivatives and MurA enzyme towards fullerene-based drug discovery.

SUBMITTER: Teimouri M

PROVIDER: S-EPMC5512856 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Structural insight into the binding of C60-derivatives with enoyl-pyruvate transferase from Helicobacter pylori.

Teimouri Mohammad M Junaid Muhammad M Khan Abbas A Zhang Houjin H

Bioinformation 20170630 6

Helicobacter pylori (H. pylori) is a human pathogen associated with acute gastritis and peptic ulcer. The MurA enzyme is an important drug target for the identification of ligands with improved efficacy and acceptable pharmaco-kinetic properties. We developed a homology model of H. Pylori MurA followed by refinement and molecular dynamics (MD) simulations. A total of 16 C60-derivatives were docked and its docking score were compared. Some of the known inhibitors were also similarly characterized ...[more]

PMID: 28729760

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Project description:Serine hydroxymethyltransferase (SHMT), encoded by the glyA gene, is a ubiquitous pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the formation of glycine from serine. The thereby generated 5,10-methylene tetrahydrofolate (MTHF) is a major source of cellular one-carbon units and a key intermediate in thymidylate biosynthesis. While in virtually all eukaryotic and many bacterial systems thymidylate synthase ThyA, SHMT and dihydrofolate reductase (DHFR) are part of the thymidylate/folate cycle, the situation is different in organisms using flavin-dependent thymidylate synthase ThyX. Here the distinct catalytic reaction directly produces tetrahydrofolate (THF) and consequently in most ThyX-containing organisms, DHFR is absent. While the resulting influence on the folate metabolism of ThyX-containing bacteria is not fully understood, the presence of ThyX may provide growth benefits under conditions where the level of reduced folate derivatives is compromised. Interestingly, the third key enzyme implicated in generation of MTHF, serine hydroxymethyltransferase (SHMT), has a universal phylogenetic distribution, but remains understudied in ThyX-containg bacteria. To obtain functional insight into these ThyX-dependent thymidylate/folate cycles, we characterized the predicted SHMT from the ThyX-containing bacterium Helicobacter pylori. Serine hydroxymethyltransferase activity was confirmed by functional genetic complementation of a glyA-inactivated E. coli strain. A H. pylori ΔglyA strain was obtained, but exhibited markedly slowed growth and had lost the virulence factor CagA. Biochemical and spectroscopic evidence indicated formation of a characteristic enzyme-PLP-glycine-folate complex and revealed unexpectedly weak binding affinity of PLP. The three-dimensional structure of the H. pylori SHMT apoprotein was determined at 2.8Ǻ resolution, suggesting a structural basis for the low affinity of the enzyme for its cofactor. Stabilization of the proposed inactive configuration using small molecules has potential to provide a specific way for inhibiting HpSHMT.

Dataset Information

Structural insight into the binding of C60-derivatives with enoyl-pyruvate transferase from Helicobacter pylori.

Publications

Structural insight into the binding of C60-derivatives with enoyl-pyruvate transferase from Helicobacter pylori.

Similar Datasets

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