Lac Operon

M��ller-hill, B.

doi:10.1002/047120918x.emb0824

Cited by 4 publications

(7 citation statements)

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“…A key feature of P lac regulation, the mechanism of repression by Lac repressor, has remained unresolved in spite of decades of research (Gralla, 1996; Muller‐Hill, 1998, 2004; Rojo, 1999; Hsu, 2002; Wilson et al , 2007). A variety of experimental results (Majors, 1975; Nick and Gilbert, 1985; Schlax et al , 1995) are consistent with a mechanism in which Lac repressor shuts off transcription by competing with RNAP for binding at the promoter.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules

et al. 2011

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The molecular basis for regulation of lactose metabolism in Escherichia coli is well studied. Nonetheless, the physical mechanism by which the Lac repressor protein prevents transcription of the lactose promoter remains unresolved. Using multi-wavelength single-molecule fluorescence microscopy, we visualized individual complexes of fluorescently tagged RNA polymerase holoenzyme bound to promoter DNA. Quantitative analysis of the single-molecule observations, including use of a novel statistical partitioning approach, reveals highly kinetically stable binding of polymerase to two different sites on the DNA, only one of which leads to transcription. Addition of Lac repressor directly demonstrates that bound repressor prevents the formation of transcriptionally productive open promoter complexes; discrepancies in earlier studies may be attributable to transcriptionally inactive polymerase binding. The single-molecule statistical partitioning approach is broadly applicable to elucidating mechanisms of regulatory systems including those that are kinetically rather than thermodynamically controlled.

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Section: Introductionmentioning

confidence: 99%

Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules

et al. 2011

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“…β-Galactosidase, the product of the Z gene of the lac operon of Escherichia coli, has a rich history in molecular biology and biochemistry (1)(2)(3). It was through the study of the appearance of this enzyme as an adaptive response to a new food source that Jacob and Monod formulated their operon model for gene expression (4).…”

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confidence: 99%

A Structural View of the Action ofEscherichia coli(lacZ) β-Galactosidase^,

et al. 2001

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The structures of a series of complexes designed to mimic intermediates along the reaction coordinate for beta-galactosidase are presented. These complexes clarify and enhance previous proposals regarding the catalytic mechanism. The nucleophile, Glu537, is seen to covalently bind to the galactosyl moiety. Of the two potential acids, Mg(2+) and Glu461, the latter is in better position to directly assist in leaving group departure, suggesting that the metal ion acts in a secondary role. A sodium ion plays a part in substrate binding by directly ligating the galactosyl 6-hydroxyl. The proposed reaction coordinate involves the movement of the galactosyl moiety deep into the active site pocket. For those ligands that do bind deeply there is an associated conformational change in which residues within loop 794-804 move up to 10 A closer to the site of binding. In some cases this can be inhibited by the binding of additional ligands. The resulting restricted access to the intermediate helps to explain why allolactose, the natural inducer for the lac operon, is the preferred product of transglycosylation.

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“…The lac operon has been studied for over a half-century, since the Nobel prize-winning work of Jacob and Monod 54 that established the concept of gene regulation. As a representative example of transcription negatively regulated by a repressor, the lac operon only produces the enzymes necessary for the metabolism of lactose in the presence of an inducer (lactose); see Müller-Hill 55 for a detailed historical account. Mechanistic models of varying complexity have been proposed to provide mathematical descriptions of the lac operon, which range from modeling just a few key components 56 , 57 to capturing the dynamics of a larger network, e.g., 5–10 system components.…”

Section: Resultsmentioning

confidence: 99%

Estimating and Assessing Differential Equation Models with Time-Course Data

2023

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Ordinary differential equation (ODE) models are widely used to describe chemical or biological processes. This Article considers the estimation and assessment of such models on the basis of time-course data. Due to experimental limitations, timecourse data are often noisy, and some components of the system may not be observed. Furthermore, the computational demands of numerical integration have hindered the widespread adoption of time-course analysis using ODEs. To address these challenges, we explore the efficacy of the recently developed MAGI (MAnifoldconstrained Gaussian process Inference) method for ODE inference. First, via a range of examples we show that MAGI is capable of inferring the parameters and system trajectories, including unobserved components, with appropriate uncertainty quantification. Second, we illustrate how MAGI can be used to assess and select different ODE models with time-course data based on MAGI's efficient computation of model predictions. Overall, we believe MAGI is a useful method for the analysis of time-course data in the context of ODE models, which bypasses the need for any numerical integration.

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Lac Operon

Cited by 4 publications

References 8 publications

Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules

Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules

A Structural View of the Action ofEscherichia coli(lacZ) β-Galactosidase^,

Estimating and Assessing Differential Equation Models with Time-Course Data

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Lac Operon

Cited by 4 publications

References 8 publications

Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules

Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules

A Structural View of the Action ofEscherichia coli(lacZ) β-Galactosidase,

Estimating and Assessing Differential Equation Models with Time-Course Data

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A Structural View of the Action ofEscherichia coli(lacZ) β-Galactosidase^,