RNA Polymerase Reaction in Bacteria

Jun, Sung Hoon; Warner, Brittany A.; Murakami, Katsuhiko

doi:10.1016/b978-0-12-378630-2.00629-0

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…Bacterial RNAP core enzyme is the simplest and best characterized form, consisting of α (two copies), β, β', and ω subunits ( Figure 1 and Figure 2 a). The core enzyme is responsible for binding to template DNA to synthesize RNA, which is complemented by a σ factor to form a holoenzyme that recognizes the promoter sequence to begin promoter-specific transcription [ 1 , 2 ].…”

Section: Early Research On the Structure Of Bacterial Rna Polymeramentioning

confidence: 99%

Structural Biology of Bacterial RNA Polymerase

Murakami

2015

Biomolecules

113

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Abstract:Since its discovery and characterization in the early 1960s (Hurwitz, J. The discovery of RNA polymerase. J. Biol. Chem. 2005, 280, 42477-42485), an enormous amount of biochemical, biophysical and genetic data has been collected on bacterial RNA polymerase (RNAP). In the late 1990s, structural information pertaining to bacterial RNAP has emerged that provided unprecedented insights into the function and mechanism of RNA transcription. In this review, I list all structures related to bacterial RNAP (as determined by X-ray crystallography and NMR methods available from the Protein Data Bank), describe their contributions to bacterial transcription research and discuss the role that small molecules play in inhibiting bacterial RNA transcription.

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Section: Early Research On the Structure Of Bacterial Rna Polymeramentioning

confidence: 99%

Structural Biology of Bacterial RNA Polymerase

Murakami

2015

Biomolecules

113

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“…Bacterial RNAP is essential for gene expression, cell growth, and viability . The bacterial RNAP core enzyme, consisting of α (two copies), β, β′, and ω subunits, is responsible for binding to DNA template and subsequent RNA synthesis and is complemented by a σ factor to start promoter-specific transcription . The molecular shape of a bacterial core RNAP resembles a crab claw, with two pincers that clamp around an RNA/DNA assembly during transcription .…”

Section: Introductionmentioning

confidence: 99%

“…5 The bacterial RNAP core enzyme, consisting of α (two copies), β, β′, and ω subunits, is responsible for binding to DNA template and subsequent RNA synthesis and is complemented by a σ factor to start promoter-specific transcription. 6 The molecular shape of a bacterial core RNAP resembles a crab claw, with two pincers that clamp around an RNA/DNA assembly during transcription. 7 The larger pincer of RNAP, the DNA binding clamp, is mainly formed by the β′ subunit and connects to the rest of RNAP via a flexible hinge at the clamp's base, composed of so-called "switches".…”

Section: ■ Introductionmentioning

confidence: 99%

X-ray Crystal Structures of Escherichia coli RNA Polymerase with Switch Region Binding Inhibitors Enable Rational Design of Squaramides with an Improved Fraction Unbound to Human Plasma Protein

et al. 2015

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Squaramides constitute a novel class of RNA polymerase inhibitors of which genetic evidence and computational modeling previously have suggested an inhibitory mechanism mediated by binding to the RNA polymerase switch region. An iterative chemistry program increased the fraction unbound to human plasma protein from below minimum detection levels, i.e. <1%, to 4~6%, while retaining biochemical potency. Since in vitro antimicrobial activity against an efflux-negative strain of Haemophilus influenzae was 4~8-fold higher, the combined improvement was at least 20~60-fold. Co-crystal structures of Escherichia coli RNA polymerase with two key squaramides showed displacement of the switch 2, predicted to interfere with the conformational change of clamp domain and/or with binding of non-template DNA, a mechanism akin to that of natural product myxopyronin. Furthermore, the structures confirmed the chemical features required for biochemical potency. The terminal isoxazole and benzyl rings bind into distinct relatively narrow, hydrophobic pockets and both are required for biochemical potency. In contrast, the linker composed of squarate and piperidine accesses different conformations in their respective co-crystal structures with RNA polymerase, reflecting its main role of proper orientation of the aforementioned terminal rings. These observations further explain the tolerance of hydrophilic substitutions in the linker region that was exploited to improve the fraction unbound to human plasma protein while retaining biochemical potency.

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