scholarly journals To Investigate the Relationship between Substrates of the N-end Rule Pathway and Genes Regulated by EBP Binding Sites (GCCGCC) in Arabidopsis thaliana

2015 ◽  
Vol 29 ◽  
pp. 296-297
Author(s):  
Geeta Prasad ◽  
Guillermina Mendiondo ◽  
Jorge V. Conde ◽  
Cristina Sousa Correia ◽  
M.J. Holdsworth
Keyword(s):  
Arabidopsis Thaliana ◽  
Binding Sites ◽  
The Relationship

scholarly journals Prediction of genome-wide effects of single nucleotide variants on transcription factor binding

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sebastian Carrasco Pro ◽  
Katia Bulekova ◽  
Brian Gregor ◽  
Adam Labadorf ◽  
Juan Ignacio Fuxman Bass
Keyword(s):  
Binding Sites ◽  
Cancer Type ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
The Impact ◽  
The Relationship

Abstract Single nucleotide variants (SNVs) located in transcriptional regulatory regions can result in gene expression changes that lead to adaptive or detrimental phenotypic outcomes. Here, we predict gain or loss of binding sites for 741 transcription factors (TFs) across the human genome. We calculated ‘gainability’ and ‘disruptability’ scores for each TF that represent the likelihood of binding sites being created or disrupted, respectively. We found that functional cis-eQTL SNVs are more likely to alter TF binding sites than rare SNVs in the human population. In addition, we show that cancer somatic mutations have different effects on TF binding sites from different TF families on a cancer-type basis. Finally, we discuss the relationship between these results and cancer mutational signatures. Altogether, we provide a blueprint to study the impact of SNVs derived from genetic variation or disease association on TF binding to gene regulatory regions.

scholarly journals Interaction of calcium ions and salivary acidic proline-rich proteins with hydroxyapatite. A possible aspect of inhibition of hydroxyapatite formation

1983 ◽  
Vol 213 (1) ◽  
pp. 11-20 ◽  
Author(s):  
A Bennick ◽  
D Kells ◽  
G Madapallimattam
Keyword(s):  
Crystal Growth ◽  
Calcium Ions ◽  
Binding Sites ◽  
Protein C ◽  
Tryptic Peptide ◽  
Protein A ◽  
Additional Amount ◽  
The Relationship ◽  
Surrounding Liquid ◽  
Hydroxyapatite Formation

The relationship between Ca2+- and hydroxyapatite-binding sites in salivary acidic proline-rich phosphoproteins A and C was investigated. Coating of hydroxyapatite with protein before adsorption had no effect on Ca2+ binding to the mineral, but simultaneous adsorption of Ca+ and protein to hydroxyapatite caused additional Ca2+ binding to the solid. The additional amount of Ca2+ adsorbed, measured in mol of Ca2+/mol of protein adsorbed to hydroxyapatite, was approx. 2 for protein C, 4 for protein A, 9 for the N-terminal tryptic peptide and 2 for dephosphorylated protein A. It is suggested that the ability of the proteins to inhibit hydroxyapatite formation is related to the binding of the proteins to crystal growth sites on the mineral, which prevents access of Ca2+ from the surrounding liquid.

scholarly journals Effects of dl-2-bromopalmitoyl-CoA and bromoacetyl-CoA in rat liver and heart mitochondria. Inhibition of carnitine palmitoyltransferase and displacement of [14C]malonyl-CoA from mitochondrial binding sites

1985 ◽  
Vol 230 (1) ◽  
pp. 169-179 ◽  
Author(s):  
M R Edwards ◽  
M I Bird ◽  
E D Saggerson
Keyword(s):  
Binding Site ◽  
Rat Liver ◽  
Binding Sites ◽  
Liver Mitochondria ◽  
Carnitine Palmitoyltransferase ◽  
Heart Mitochondria ◽  
Nitrobenzoic Acid ◽  
Malonyl Coa ◽  
Tissue Differences ◽  
The Relationship

The overt form of carnitine palmitoyltransferase (CPT1) in rat liver and heart mitochondria was inhibited by DL-2-bromopalmitoyl-CoA and bromoacetyl-CoA. S-Methanesulphonyl-CoA inhibited liver CPT1. The inhibitory potency of DL-2-bromopalmitoyl-CoA was 17 times greater with liver than with heart CPT1. Inhibition of CPT1 by DL-2-bromopalmitoyl-CoA was unaffected by 5,5′-dithiobis-(2-nitrobenzoic acid) or (in liver) by starvation. In experiments in which DL-2-bromopalmitoyl-CoA displaced [14C]malonyl-CoA bound to liver mitochondria, the KD (competing) was 25 times the IC50 for inhibition of CPT1 providing evidence that the malonyl-CoA-binding site is unlikely to be the same as the acyl-CoA substrate site. Bromoacetyl-CoA inhibition of CPT1 was more potent in heart than in liver mitochondria and was diminished by 5,5′-dithiobis-(2-nitrobenzoic acid) or (in liver) by starvation. Bromoacetyl-CoA displaced bound [14C]malonyl-CoA from heart and liver mitochondria. In heart mitochondria this displacement was competitive with malonyl-CoA and was considerably facilitated by L-carnitine. In liver mitochondria this synergism between carnitine and bromoacetyl-CoA was not observed. It is suggested that bromoacetyl-CoA interacts with the malonyl-CoA-binding site of CPT1. L-Carnitine also facilitated the displacement by DL-2-bromopalmitoyl-CoA of [14C]malonyl-CoA from heart, but not from liver, mitochondria. DL-2-Bromopalmitoyl-CoA and bromoacetyl-CoA also inhibited overt carnitine octanoyl-transferase in liver and heart mitochondria. These findings are discussed in relation to inter-tissue differences in (a) the response of CPT1 activity to various inhibitors and (b) the relationship between high-affinity malonyl-CoA-binding sites and those sites for binding of L-carnitine and acyl-CoA substrates.

scholarly journals Visualization of intracellular concanavalin A binding sites in retinal photoreceptors.

1978 ◽  
Vol 26 (10) ◽  
pp. 822-828 ◽  
Author(s):  
I Nir
Keyword(s):  
Concanavalin A ◽  
Binding Sites ◽  
Photoreceptor Cells ◽  
Con A ◽  
Thin Sections ◽  
Glycol Methacrylate ◽  
Outer Segments ◽  
Retinal Photoreceptors ◽  
Carbohydrate Components ◽  
The Relationship

Localization of carbohydrate components in retinal photoreceptor cells and membranes was studied. Frog and rat retinas were fixed with glutaraldehyde and embedded in glycol methacrylate or in a mixture of glycol methacrylate, glutaraldehyde and urea. Thin sections were incubated with ferritin-labeled concanavalin A (F-Con A) and stained with osmium vapors. Intensive binding was observed in both rod and cone outer segments. In the rod inner segment, differential binding of F-Con A was demonstrated. While numerous ferritin granules were observed in the myoid zone, only a few were seen in the ellipsoid zone, except for a local accumulation along the plasma membrane. In the rod outer segment, Con A binding sites were closely associated with the disk membranes. Ferritin granules were observed on both sides of the membranes. The relationship between the localization of Con A binding sites and the orientation of visual pigment molecules within the rod outer segments disk membranes was discussed.

scholarly journals DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of enhancers

2021 ◽  
Author(s):  
Bernardo P de Almeida ◽  
Franziska Reiter ◽  
Michaela Pagani ◽  
Alexander Stark
Keyword(s):  
Dna Sequence ◽  
Binding Sites ◽  
De Novo ◽  
De Novo Design ◽  
Flanking Sequence ◽  
Enhancer Activity ◽  
Drosophila Melanogaster S2 Cells ◽  
Enhancer Sequences ◽  
The Relationship ◽  
Deep Learning Model

Enhancer sequences control gene expression and comprise binding sites (motifs) for different transcription factors (TFs). Despite extensive genetic and computational studies, the relationship between DNA sequence and regulatory activity is poorly understood and enhancer de novo design is considered impossible. Here we built a deep learning model, DeepSTARR, to quantitatively predict the activities of thousands of developmental and housekeeping enhancers directly from DNA sequence in Drosophila melanogaster S2 cells. The model learned relevant TF motifs and higher-order syntax rules, including functionally non-equivalent instances of the same TF motif that are determined by motif-flanking sequence and inter-motif distances. We validated these rules experimentally and demonstrated their conservation in human by testing more than 40,000 wildtype and mutant Drosophila and human enhancers. Finally, we designed and functionally validated synthetic enhancers with desired activities de novo.

scholarly journals The Regulation of Haemocyanin Oxygen Affinity During Emersion of the Crayfish Austropotamobius Pallipes: III. The Dependence of Ca2+-Haemocyanin Binding on the Concentration Of L-Lactate

1987 ◽  
Vol 133 (1) ◽  
pp. 339-352
Author(s):  
S. MORRIS ◽  
C.R. BRIDGES ◽  
M. K. GRIESHABER
Keyword(s):  
Biological Sciences ◽  
Binding Sites ◽  
Lactate Concentration ◽  
Oxygen Affinity ◽  
Calcium Lactate ◽  
Worst Case ◽  
Austropotamobius Pallipes ◽  
University Of Calgary ◽  
Lactate Formation ◽  
The Relationship

The binding of Ca2+ to the haemocyanin of the crayfish Austropotamobius pallipes was investigated. The amount of bound Ca2+ was determined using an ultrafiltration technique to produce haemocyanin-free solutions, the Ca2+ concentration of which could then be compared with that of the original, unfiltered solution. Any difference between the two values would indicate the amount of calcium bound by haemocyanin. The effect of L-lactate on Ca2+ binding was investigated by determining the amount of bound ion at different concentrations of L-lactate. In addition, oxygen equilibrium curves were constructed for some of the solutions to verify that the haemocyanin oxygen affinity remained sensitive to L-lactate and to determine whether the haemocyanin was functionally similar to that used in previous investigations. With 17 mmol 1−1 total Ca2+ and approximately 1 mmol 1−1 L-lactate the number of Ca2+ binding sites was estimated to be between eight and nine per haemocyanin molecule. Without taking into account the formation of calcium lactate, the observed dependency of Ca2+-haemocyanin binding on L-lactate concentration could best be described by the equation: Ca2+/Hc = 8.64-0.32[lactate−]. A ‘worst case’ estimate for maximum calcium lactate formation, assuming Ca2+ to be the only counterion available to lactate, altered the relationship slightly to: Ca2+/Hc = 8.65-0.35[lactate−]. Note: Present address: Department of Biological Sciences, University of Calgary, 2500 University Drive N/V, Calgary, Alberta, Canada T2N 1N4.

scholarly journals Natriuretic peptide receptors in the kidney and the ventral and dorsal aortae of the Atlantic hagfish Myxine glutinosa (Agnatha).

1995 ◽  
Vol 198 (9) ◽  
pp. 1875-1882 ◽  
Author(s):  
T Toop ◽  
J A Donald ◽  
D H Evans
Keyword(s):  
Natriuretic Peptide ◽  
Binding Sites ◽  
Kidney Tissue ◽  
Peptide Receptors ◽  
Natriuretic Peptide Receptors ◽  
Myxine Glutinosa ◽  
Clearance Receptor ◽  
Relationship Of ◽  
The Relationship ◽  
Gmp Production

The character of natriuretic peptide receptors (NPRs) in the kidney and aortae of the Atlantic hagfish Myxine glutinosa was determined and compared with that of NPRs in hagfish gills. The relationship of hagfish kidney and aortic NPRs with NPRs from higher vertebrates was also examined. Iodinated atrial and C-type natriuretic peptides (NPs) (125I-ANP, 125I-CNP) were used in tissue section autoradiography, competition studies and guanylate cyclase (GC) assays. Rat atrial and porcine C-type NPs (rANP, pCNP) and rat des[Gln18, Ser19, Gly20, Leu21 Gly22]ANP-(4-23)-NH2 (C-ANF, which binds to the mammalian and teleost 'clearance' receptor, NPR-C), were used as competing ligands. 125I-ANP binding sites were observed on both aortae and on the glomeruli, neck segments and archinephric ducts of the kidney. 4.0 nmol l-1 rANP competed for 50% of 125I-ANP glomerular sites. 125I-CNP did not visibly bind to any of the tissues, but 300 nmol l-1 pCNP competed for 50% of 125I-ANP glomerular sites. C-ANF failed to compete for 125I-ANP sites. rANP and pCNP stimulated cyclic GMP production in kidney membrane preparations, but C-ANF did not, demonstrating that the hagfish kidney NPR is GC-linked. This study suggests that a predominant population of ANP-like receptors, similar to the mammalian NPR-A, exists in the myxinoid aortae and kidney tissue. However, no detectable population of a receptor that binds all NPs, such as is present in the hagfish gill, nor an NPR similar to the NPR-C of higher vertebrates was discovered.

scholarly journals Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Erin A Clark ◽  
Michael Rutlin ◽  
Lucia Capano ◽  
Samuel Aviles ◽  
Jordan R Saadon ◽  
...  
Keyword(s):  
Binding Sites ◽  
Binding Capacity ◽  
Chromatin Accessibility ◽  
Excitatory Input ◽  
Orphan Receptor ◽  
Knock Out ◽  
Putative Target ◽  
Layer 4 ◽  
The Relationship ◽  
Receptor Beta

Retinoic acid-related orphan receptor beta (RORβ) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is largely unknown. We find RORβ is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age in wildtype mice. Loss of RORβ delays excitatory input and disrupts gene expression and chromatin accessibility, with down-regulation of L4 and up-regulation of L5 genes, suggesting a disruption in cellular specification. Expression and binding site accessibility change for many other TFs, including closure of neurodevelopmental TF binding sites and increased expression and binding capacity of activity-regulated TFs. Lastly, a putative target of RORβ, Thsd7a, is down-regulated without RORβ, and Thsd7a knock-out alone disrupts TCA organization in adult barrels.

scholarly journals Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746

2016 ◽  
Vol 37 (3) ◽  
pp. 1095-1107 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Beata Planeta ◽  
Nabeel Nabulsi ◽  
Donna Palumbo ◽  
Xiaoxi Li ◽  
...  
Keyword(s):  
Binding Sites ◽  
Human Subjects ◽  
Receptor Occupancy ◽  
Healthy Human ◽  
Positron Emission ◽  
Relationship Of ◽  
The Relationship ◽  
Pet Scans

Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds “tracer” levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [11C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [11C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%–97% and 30%–93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%–15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

scholarly journals Covalent labelling of ligand binding sites of human placental S-adenosylhomocysteine hydrolase with 8-azido derivatives of adenosine and cyclic AMP

1985 ◽  
Vol 232 (3) ◽  
pp. 643-650 ◽  
Author(s):  
V N Aiyar ◽  
M S Hershfield
Keyword(s):  
Cyclic Amp ◽  
Binding Sites ◽  
Catalytic Mechanism ◽  
Periodate Oxidation ◽  
Regulatory Subunit ◽  
Adenosylhomocysteine Hydrolase ◽  
Dependent Protein ◽  
Covalently Linked ◽  
The Relationship ◽  
Derivatives Of

S-Adenosylhomocysteine hydrolase (AdoHcyase) has previously been identified as a cytoplasmic adenosine and cyclic AMP binding protein. In order to examine the relationship between the adenosine and cyclic AMP binding sites on this enzyme we have explored the use of 8-azido analogues of adenosine and cyclic AMP as photoaffinity reagents for covalently labelling AdoHcyase purified from human placenta. 8-Azidoadenosine (8-N3-Ado), like adenosine, inactivated AdoHcyase, and the rate of inactivation was greatly increased by periodate oxidation. In addition, 8-N3-Ado was found to participate in the first step in the catalytic mechanism for AdoHcyase, resulting in conversion of enzyme-bound NAD+ to NADH, although it was not a substrate for the full enzyme-catalysed reaction. Radioactively labelled 8-N3-Ado, its periodate-oxidized derivative and 8-azidoadenosine 3′, 5′-phosphate (8-N3-cAMP) bound specifically to adenosine binding sites on AdoHcyase and, after irradiation, became covalently linked to the enzyme. Photoaffinity-labelled enzyme could be precipitated by monoclonal antibody to human AdoHcyase. Two observations suggested that cyclic AMP and adenosine bind to the same sites on AdoHcyase. First cyclic AMP and adenosine each blocked binding of both radioactively labelled 8-N3-Ado and 8-N3-cAMP, and second, digestion with V8 proteinase generated identical patterns of peptides from AdoHcyase that had been photolabelled with [32P]8-N3-cAMP and [3H]8-N3-Ado. Binding sites for cyclic AMP on AdoHcyase were found to differ functionally and structurally from cyclic AMP binding sites on the R1 regulatory subunit of cyclic AMP-dependent protein kinase.

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