P. S.

Wilkinson, Tim

doi:10.1093/nq/s1-ix.226.184f

Cited by 4 publications

(7 citation statements)

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“…Endotoxins have also been incriminated in the production of acute hepatic failure (33). The present studies demonstrate that acute administration of endotoxin during late pregnancy decreases rat hepatic microsomal mixed-function oxidase enzyme activities.…”

Section: Discussionsupporting

confidence: 51%

Gram-Negative Endotoxin Administration Decreases Hepatic Drug-Metabolizing Enzymes during Development in Rats

Sonawane

Yaffe

1980

Pediatr Res

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SummaryThe frequency of gram-negative infections and endotoxemia in the perinatal period prompted an investigation of the effects of endotoxin (Escherichia coli 026B6) on hepatic drug metabolism. Gravid female rats given injections IP with different dosages of lipopolysaccharide during late pregnancy resulted in significant de~ression of the liver microsomal cvtochrome P-450 dewndent monooxygenase activities. The acute-administration of enhotoxin to mothers (1.4 mg/kg on seventh day after parturition) significantly decreased the hepatic activity of aminopyrine demethylase and contents of cytochrome P-450 of suckling neonates and mothers. However, chronic administration of endotoxin (0.2 mg/kg/ day for 7 days) to lactating mothers did not alter neonatal enzyme activities. When neonates themselves were given injections of endotoxin (1.0 mg/kg) a t 7, 16, and 27 days of age, a significant reduction in levels of mixed function oxidase enzymes was observed. These observations suggest that the ability of mothers and neonates to metabolize drugs is significantly decreased upon exposure to endotoxin, and this demands careful evaluation of drug disposition studies in gram-negative sepsis. Speculation

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Section: Discussionsupporting

confidence: 51%

Gram-Negative Endotoxin Administration Decreases Hepatic Drug-Metabolizing Enzymes during Development in Rats

Sonawane

Yaffe

1980

Pediatr Res

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“…Estimation of the content of the asymmetric unit (ASU) suggested that three or four His-tagged AbsC subunits were most likely, giving solvent contents of 60.3% or 47.0% and crystal-packing parameters (V M ) of 3.09 or 2.32 Å 3 Da À1 , respectively. Given that both DLS and gel filtration suggest that AbsC is dimeric and that MarR homologues exist as homodimers (Wilkinson & Grove, 2006), an even number of subunits per ASU, i.e. four, would seem to be the most probable (Matthews, 1968).…”

Section: Resultsmentioning

confidence: 99%

“…The resultant cellular responses are frequently triggered by the binding of small signalling molecules to regulatory proteins. The activities of the MarR family of transcriptional regulators are thought to be modulated in this way (Wilkinson & Grove, 2006). These cytoplasmic proteins control a variety of biological functions in bacteria, including antibiotic resistance (Miller & Sulavik, 1996;Alekshun et al, 2001), the response to oxidative stress (Spory et al, 2002;Wilkinson & Grove, 2004) and the synthesis of pathogenic factors (Rouanet et al, 2004;Wyborn et al, 2004), and thus they are of significant clinical interest.…”

Section: Introductionmentioning

confidence: 99%

“…These cytoplasmic proteins control a variety of biological functions in bacteria, including antibiotic resistance (Miller & Sulavik, 1996;Alekshun et al, 2001), the response to oxidative stress (Spory et al, 2002;Wilkinson & Grove, 2004) and the synthesis of pathogenic factors (Rouanet et al, 2004;Wyborn et al, 2004), and thus they are of significant clinical interest. They exist in solution as homodimers and control gene expression by interacting with palindromic (or pseudopalindromic) DNA sequences through conserved winged-helix DNA-binding motifs (Wilkinson & Grove, 2006). Although the structures of several MarR family members are now known (Wilkinson & Grove, 2006), only the MarR structure has been determined with a bound ligand, namely salicylate (Alekshun et al, 2001), and only the OhrR structure has been determined bound to DNA (Hong et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…They exist in solution as homodimers and control gene expression by interacting with palindromic (or pseudopalindromic) DNA sequences through conserved winged-helix DNA-binding motifs (Wilkinson & Grove, 2006). Although the structures of several MarR family members are now known (Wilkinson & Grove, 2006), only the MarR structure has been determined with a bound ligand, namely salicylate (Alekshun et al, 2001), and only the OhrR structure has been determined bound to DNA (Hong et al, 2005). The absC gene (antibiotic synthesis deficient) encodes a novel pleiotropic regulator of antibiotic synthesis in Streptomyces coelicolor that belongs to the MarR family (Kock, Mootien & Bibb, unpublished results).…”

Section: Introductionmentioning

confidence: 99%

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Crystallization and preliminary X-ray analysis of AbsC, a novel regulator of antibiotic production inStreptomyces coelicolor

et al. 2007

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Crystals of recombinant AbsC (subunit MW = 18 313 Da; 158 amino acids), a novel regulator of antibiotic production from Streptomyces coelicolor, were grown by vapour diffusion. The protein crystallizes in space group P2 1 2 1 2 1 , with unit-cell parameters a = 43.53, b = 121.30, c = 143.75 Å . Native data to a resolution of 2.25 Å were recorded at station PX 14.1 (Daresbury) from a single crystal. Preliminary analysis of these data suggests that the asymmetric unit contains four copies of the AbsC monomer, giving an estimated solvent content of 47.0%. AbsC belongs to the MarR family of proteins that mediate ligandresponsive transcriptional control.

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An Environmental DNA‐Derived Type II Polyketide Biosynthetic Pathway Encodes the Biosynthesis of the Pentacyclic Polyketide Erdacin

2009

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Environmental DNA-derived cosmid clones containing type II polyketide synthase genes were screened for the ability to produce clone-specific metabolites in Streptomyces. One of the Streptomyces recombinants produces erdacin, a novel polyketide with a previously unknown pentacyclic skeleton. Erdacin provides tangible evidence that environmental DNA gene clusters are likely to encode the biosynthesis of molecules that are substantively different from those that have been identified using culture-based strategies.

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P. S.

Cited by 4 publications

References 0 publications

Gram-Negative Endotoxin Administration Decreases Hepatic Drug-Metabolizing Enzymes during Development in Rats

Gram-Negative Endotoxin Administration Decreases Hepatic Drug-Metabolizing Enzymes during Development in Rats

Crystallization and preliminary X-ray analysis of AbsC, a novel regulator of antibiotic production inStreptomyces coelicolor

An Environmental DNA‐Derived Type II Polyketide Biosynthetic Pathway Encodes the Biosynthesis of the Pentacyclic Polyketide Erdacin

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