Faculty Opinions recommendation of Allosteric Effector ppGpp Potentiates the Inhibition of Transcript Initiation by DksA.

2018 ◽  
Author(s):  
Mark Paget
Keyword(s):  
Allosteric Effector ◽  
Transcript Initiation

scholarly journals Allosteric Effector ppGpp Potentiates the Inhibition of Transcript Initiation by DksA

2018 ◽  
Vol 69 (5) ◽  
pp. 828-839.e5 ◽  
Author(s):  
Vadim Molodtsov ◽  
Elena Sineva ◽  
Lu Zhang ◽  
Xuhui Huang ◽  
Michael Cashel ◽  
...  
Keyword(s):  
Allosteric Effector ◽  
Transcript Initiation

scholarly journals Allosteric effector ppGpp potentiates the inhibition of transcript initiation by DksA

2017 ◽  
Author(s):  
Vadim Molodtsov ◽  
Elena Sineva ◽  
Lu Zhang ◽  
Xuhui Huang ◽  
Michael Cashel ◽  
...  
Keyword(s):  
Dna Binding ◽  
Rna Polymerase ◽  
Stringent Response ◽  
Structural Data ◽  
Binding Mode ◽  
List Type ◽  
Template Strand ◽  
Transcriptional Inhibition ◽  
Allosteric Effector ◽  
Transcript Initiation

SUMMARYDksA and ppGpp are the central players in the Escherichia coli stringent response and mediate a complete reprogramming of the transcriptome from one optimized for rapid growth to one adapted for survival during nutrient limitation. A major component of the response is a reduction in ribosome synthesis, which is accomplished by the synergistic action of DksA and ppGpp bound to RNA polymerase (RNAP) inhibiting transcription of rRNAs. Here, we report the X-ray crystal structures of E. coli RNAP holoenzyme in complex with DksA alone and with ppGpp. The structures show that DksA accesses the template strand at the active site and the downstream DNA binding site of RNAP simultaneously and reveal that binding of the allosteric effector ppGpp reshapes the RNAP–DksA complex. The structural data support a model for transcriptional inhibition in which ppGpp potentiates the destabilization of open complexes on rRNA promoters by DksA. We also determined the structure of RNAP–TraR complex, which reveals the mechanism of ppGpp-independent transcription inhibition by TraR. This work establishes new ground for understanding the pleiotropic effects of DksA and ppGpp on transcriptional regulation in proteobacteria.HighlightsDksA has two modes of binding to RNA polymeraseDksA is capable of inhibiting the catalysis and influences the DNA binding of RNAPppGpp acts as an allosteric effector of DksA functionppGpp stabilizes DksA in a more functionally important binding mode

scholarly journals Characterization of the Overlapping Promoters of nolB and nolW, Two Soybean Cultivar Specificity Genes from Rhizobium fredii Strain USDA257

1997 ◽  
Vol 10 (1) ◽  
pp. 138-141 ◽  
Author(s):  
Jun Gu ◽  
Pedro A. Balatti ◽  
Hari B. Krishnan ◽  
Steven G. Pueppke
Keyword(s):  
Regulatory Gene ◽  
Initiation Site ◽  
Dual Control ◽  
Start Site ◽  
Rhizobium Fredii ◽  
Normal Expression ◽  
Transcript Initiation ◽  
Cultivar Specificity ◽  
Transcript Start Site

The transcripts of nolW and nolB, two divergently oriented cultivar specificity genes of Rhizobium fredii strain USDA257, are known to be initiated 14 bp apart from promoters that face one another. We show here that expression of nolB is dependent both on induction with flavonoid signals and on the regulatory gene, nodD1. Expression of nolW is constitutive and independent of flavonoids and nodD1. Normal expression of nolB is retained with a promoter that extends only 61 bp upstream of the transcript start site, but it is lost if an additional 24 bp are removed. Substantial expression of nolW is retained with a promoter that contains only 34 bp of DNA upstream from the transcript initiation site. The dual control region for the two genes is thus only about 109 bp in length.

The interaction of ligands with chemically modified phosphorylase b

1976 ◽  
Vol 54 (5) ◽  
pp. 494-499
Author(s):  
D. Brooks ◽  
S. J. W. Busby ◽  
J. R. Griffiths ◽  
G. K. Radda ◽  
O. Avramovic-Zikic
Keyword(s):  
Conformational Changes ◽  
Spin Label ◽  
Native Enzyme ◽  
Carboxyl Groups ◽  
Chemically Modified ◽  
Allosteric Effector ◽  
Spin Resonance ◽  
Label Probe ◽  
Glycine Ethyl Ester ◽  
Modified Enzyme

Phosphorylase b which had been inactivated with 5-diazo-1H-tetrazole was specifically labelled with 4-iodoacetamidosalicylic acid (a fluorescent probe) or with N-(1-oxyl-2,2,6,6,-tetramethyl-4-piperidinyl)iodoacetamide (a spin label probe) so that the binding of ligands and accompanying conformational changes could be determined by fluorescence or electron spin resonance changes, respectively. The allosteric effector, AMP, causes conformational changes similar to those caused in the native enzyme. The affinity of binding of phosphate or AMP to the inhibited protein is the same as for the unmodified protein. The heterotropic interactions between glucose-1-phosphate or glycogen and AMP are much less in the inactivated enzyme than in unmodified phosphorylase. Using a light scattering assay, it is shown that the modified enzyme binds to glycogen less strongly than the native protein.Phosphorylase b which had been inactivated by carbodiimide in the presence of glycine ethyl ester, resulting in the modification of one or more carboxyl groups, was labelled with the spin label probe described above. The modified enzyme has an affinity for AMP similar to that of the native enzyme. AMP binding to the modified enzyme is tightened by glycogen, weakened by glucose-6-phosphate and is unaffected by glucose- 1-phosphate.The actions of 5-diazo-1H-tetrazole and carbodiimide on phosphorylase are discussed in the light of the above observations.

scholarly journals A conserved C-terminal peptide of sorghum phosphoenolpyruvate carboxylase promotes its proteolysis, which is prevented by Glc-6P or the phosphorylation state of the enzyme

Planta ◽  
2021 ◽  
Vol 254 (3) ◽  
Author(s):  
Jacinto Gandullo ◽  
Rosario Álvarez ◽  
Ana-Belén Feria ◽  
José-Antonio Monreal ◽  
Isabel Díaz ◽  
...  
Keyword(s):  
Amino Acids ◽  
Phosphoenolpyruvate Carboxylase ◽  
Synthetic Peptide ◽  
Phosphorylation State ◽  
Allosteric Effector ◽  
Cathepsin Proteases ◽  
Photosynthesis Pathway

Abstract Main conclusion A synthetic peptide from the C-terminal end of C4-phosphoenolpyruvate carboxylase is implicated in the proteolysis of the enzyme, and Glc-6P or phosphorylation of the enzyme modulate this effect. Abstract Phosphoenolpyruvate carboxylase (PEPC) is a cytosolic, homotetrameric enzyme that performs a variety of functions in plants. Among them, it is primarily responsible for CO2 fixation in the C4 photosynthesis pathway (C4-PEPC). Here we show that proteolysis of C4-PEPC by cathepsin proteases present in a semi-purified PEPC fraction was enhanced by the presence of a synthetic peptide containing the last 19 amino acids from the C-terminal end of the PEPC subunit (pC19). Threonine (Thr)944 and Thr948 in the peptide are important requirements for the pC19 effect. C4-PEPC proteolysis in the presence of pC19 was prevented by the PEPC allosteric effector glucose 6-phosphate (Glc-6P) and by phosphorylation of the enzyme. The role of these elements in the regulation of PEPC proteolysis is discussed in relation to the physiological context.

RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats

1996 ◽  
Vol 271 (2) ◽  
pp. H602-H613 ◽  
Author(s):  
M. P. Kunert ◽  
J. F. Liard ◽  
D. J. Abraham
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Experimental Models ◽  
Metabolic Demand ◽  
Flow Probe ◽  
Inositol Hexaphosphate ◽  
Control Value ◽  
Allosteric Effector

Tissue O2 delivery in excess of metabolic demand may be a factor in the development of high vascular resistance in experimental models of volume-expanded hypertension. This hypothesis was previously tested in rats with an exchange transfusion of red blood cells treated with inositol hexaphosphate or an intravenous infusion of RSR-4, allosteric effectors of hemoglobin. The binding of these drugs with hemoglobin effect a conformational change in the molecule, such that the affinity for O2 is reduced. However, in both preparations, the changes in vascular resistance could have been nonspecific. The present studies used intravenous infusions of RSR-13, which did not share some of the problematic characteristics of RSR-4 and inositol hexaphosphate. Conscious instrumented rats (an electromagnetic flow probe on ascending aorta or an iliac, mesenteric, or renal Doppler flow probe) were studied for 6 h after an RSR-13 infusion of 200 mg/kg in 15 min. This dose significantly increased arterial P50 (PO2 at which hemoglobin is 50% saturated) from 38 +/- 0.8 to 58 +/- 1.4 mmHg at 1 h after the start of the infusion. In the 3rd h cardiac output fell significantly from a control value of 358 +/- 33 to 243 +/- 24 ml.kg-1.min-1 and total peripheral resistance significantly increased from 0.31 +/- 0.03 to 0.43 +/- 0.04 mmHg.ml-1.kg.min. Cardiac output and P50 returned toward control over the next few hours. Neither cardiac output nor total peripheral resistance changed in the group of rats receiving vehicle alone. In a separate group of rats, iliac flow decreased significantly to 60% of control and iliac resistance increased to 160% of control. Iliac flow increased significantly in the group of rats that received vehicle only. Although the mechanism of these changes has not been established, these results suggest that a decreased O2 affinity leads to an increased total peripheral resistance and regional vascular resistance and support the hypothesis that O2 plays a role in the metabolic autoregulation of blood flow.

scholarly journals Generation and Export of Red Blood Cell ATP in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Timothy J. McMahon ◽  
Cole C. Darrow ◽  
Brooke A. Hoehn ◽  
Hongmei Zhu
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Dynamic Control ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Antioxidant Systems ◽  
Atp Production ◽  
Allosteric Effector ◽  
The Face ◽  
Differential Control ◽  
Glucose 6 Phosphate Dehydrogenase

Metabolic homeostasis in animals depends critically on evolved mechanisms by which red blood cell (RBC) hemoglobin (Hb) senses oxygen (O2) need and responds accordingly. The entwined regulation of ATP production and antioxidant systems within the RBC also exploits Hb-based O2-sensitivity to respond to various physiologic and pathophysiologic stresses. O2 offloading, for example, promotes glycolysis in order to generate both 2,3-DPG (a negative allosteric effector of Hb O2 binding) and ATP. Alternatively, generation of the nicotinamide adenine dinucleotide phosphate (NADPH) critical for reducing systems is favored under the oxidizing conditions of O2 abundance. Dynamic control of ATP not only ensures the functional activity of ion pumps and cellular flexibility, but also contributes to the availability of vasoregulatory ATP that can be exported when necessary, for example in hypoxia or upon RBC deformation in microvessels. RBC ATP export in response to hypoxia or deformation dilates blood vessels in order to promote efficient O2 delivery. The ability of RBCs to adapt to the metabolic environment via differential control of these metabolites is impaired in the face of enzymopathies [pyruvate kinase deficiency; glucose-6-phosphate dehydrogenase (G6PD) deficiency], blood banking, diabetes mellitus, COVID-19 or sepsis, and sickle cell disease. The emerging availability of therapies capable of augmenting RBC ATP, including newly established uses of allosteric effectors and metabolite-specific additive solutions for RBC transfusates, raises the prospect of clinical interventions to optimize or correct RBC function via these metabolite delivery mechanisms.

scholarly journals Cyclic AMP downregulates c-mycexpression by inhibition of transcript initiation in human B-precursor Reh cells

FEBS Letters ◽  
1994 ◽  
Vol 337 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Kristin Brevik Andersson ◽  
Kjetil Taskén ◽  
Heidi Kill Blomhoff
Keyword(s):  
Cyclic Amp ◽  
Transcript Initiation ◽  
Reh Cells
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