Enzymic synthesis of hydroxymethyldihydropteridine Pyrophosphate and dihydrofolate

Shiota, Tetsuo; Baugh, Charles M.; Jackson, Raymond J.; Dillard, Randle

doi:10.1021/bi00840a052

Cited by 75 publications

(58 citation statements)

References 18 publications

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“…DHPS plays a vital role in the proliferation of microorganisms and it is encoded by the gene folP [7] . DHPS is involved in the conversion of 6-hydroxymethyl-7,8-dihydropteridine-pyrophosphate and para-amino benzoic acid (PABA) to pyrophosphate and 7,8-dihydropteroate [8] . PABA is synthesized through the upregulation process by the chorismate pathway and supplemented into the folate biosynthesis pathway.…”

mentioning

confidence: 99%

Ethyl Iso-allocholate from a Medicinal Rice Karungkavuni Inhibits Dihydropteroate Synthase in Escherichia coli: A Molecular Docking and Dynamics Study

Kullappan¹,

Anbarasu²,

Ramaiah³

2016

pharmaceutical-sciences

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Malathi, et al.: E. coli DHPS Inhibition by Ethyl IsoallocholateMedicinal rice varieties have defensive and therapeutic properties against many human disorders. Drug resistance has become a major problem in recent years. Escherichia coli have developed resistance to most of the antibiotics including sulfonamides that target dihydropteroate synthase. In the present study, we attempted to identify a novel inhibitor for the dihydropteroate synthase from a medicinal rice variety Karungkavuni. The phytochemical composition of the rice Karungkavuni was analysed through gas chromatography-mass spectrometry. The isolated compounds with reported antimicrobial activity were subjected to molecular docking procedures to understand the binding behaviour of the ligands with the target. These analyses revealed that ethyl iso-allocholate and 9,12,15-octadecatrienoic acid-2,3-dihydroxypropyl ester were the best binding compounds. Molecular dynamics studies revealed dihydropteroate synthase-ethyl iso-allocholate complex was more stable than other ligands throughout the simulation. Our study demonstrated that ethyl iso-allocholate isolated from Karungkavuni could serve as a potent inhibitor of dihydropteroate synthase.

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confidence: 99%

Ethyl Iso-allocholate from a Medicinal Rice Karungkavuni Inhibits Dihydropteroate Synthase in Escherichia coli: A Molecular Docking and Dynamics Study

Kullappan¹,

Anbarasu²,

Ramaiah³

2016

pharmaceutical-sciences

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“…HPPK activity was first detected in cell extracts from a number of organisms (25)(26)(27) including Escherichia coli (26,30,31). Recently, the Streptococcus pneumoniae HPPK chromosomal gene, sulD, was cloned and sequenced (20).…”

mentioning

confidence: 99%

Cloning, sequence analysis, and overexpression of Escherichia coli folK, the gene coding for 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase

et al. 1992

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The gene coding for the Escherichia coli enzyme 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase has been cloned and sequenced. This gene, designated folK, codes for a protein of 159 amino acids, including an amino-terminal methionine. The protein was overexpressed in E. coli MC4100 by cloning the gene behind the lacUVS promoter in a high-copy-number plasmid. The enzyme was purified to homogeneity. Amino-terminal analysis of the purified protein showed that the amino-terminal methionine had been removed. The compositional molecular mass (17,945 Da) was identical to the molecular mass determined by mass spectrometry. The enzyme was observed to have a large number of proline residues and migrated anomalously in sodium dodecyl sulfate-polyacrylamide gels, with an apparent molecular mass of 23,000 Da.

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“…This compound could then be dimethylated either before or after ring closure to produce dimethyl dihydroneopterin triphosphate 3. Hydrolysis of the triphosphate from this compound, followed by the loss of a C2 unit, would then generate compound 5. Compound 5 could then be converted into methanopterin by a series of reactions analogous to those known to occur in folic acid biosynthesis; i.e., it is first converted into the pyrophosphate ester wwith ATP (13,15,20) and subsequently condensed with either free 5-(p-aminophenyl)-1,2,3,4-tetrahydroxypentane or 5-(p-aminophenyl)-1,2,3,4-tetrahydroxypentane conjugated to ribose, phosphate, and oahydroxyglutaric acid (1i, 15).…”

Section: Resultsmentioning

confidence: 99%

“…1) would also indicate that these molecules are biosynthesized by similar reactions. Folic acid is known to be biosynthesized by the condensation of 6-hydroxymethyl-7,8-H2-pterin pyrophosphate with either p-aminobenzoic acid or p-aminobenzoylglutamate to produce the corresponding 7,8-dihydropteroates (13,15,20). The required substrates for the reaction, 6-hydroxymethyl-7,8-H2-pterin pyrophosphate and p-aminobenzoic acid, arise from GTP (2) and chorismic acid (21), respectively.…”

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Biosynthesis of the 7-methylated pterin of methanopterin

White¹

1986

J Bacteriol

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The incorporation of [15N]glycine and [U-methyl-2H]methionine into methanopterin by growing cells of a methanogenic bacterium was measured to establish the biosynthetic i-oute to the methylated pterin in this structure. The tetrahydromethanopterin produced by the cells was oxidatively cleaved to produce 7-methylpterin, and the amount of label incorporated into this pterin was measured by gas chromatography-mass spectrometry of the ditrimethylsilyl derivative of this compound. Approximately 27% of the 7-methylpterin and the guanine present in the cell was derived from the fed ['5N]glycine. [U-methyl-2H]methionine was incorporated with the initial retention of all three deuteriums. These results are consistent with the biosynthesis of the pterin of methanopterin originating from GTP and its 7-mnethyl group arising from the methyl group of methionine.

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Enzymic synthesis of hydroxymethyldihydropteridine Pyrophosphate and dihydrofolate

Cited by 75 publications

References 18 publications

Ethyl Iso-allocholate from a Medicinal Rice Karungkavuni Inhibits Dihydropteroate Synthase in Escherichia coli: A Molecular Docking and Dynamics Study

Ethyl Iso-allocholate from a Medicinal Rice Karungkavuni Inhibits Dihydropteroate Synthase in Escherichia coli: A Molecular Docking and Dynamics Study

Cloning, sequence analysis, and overexpression of Escherichia coli folK, the gene coding for 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase

Biosynthesis of the 7-methylated pterin of methanopterin

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