Polymorphism in exon 2 encoding the putative ligand binding pocket of the bovine insulin-like growth factor 1 receptor affects milk traits in four different cattle breeds

2016 ◽  
Vol 134 (1) ◽  
pp. 34-42 ◽  
Author(s):  
M. Szewczuk
Keyword(s):  
Growth Factor ◽  
Ligand Binding ◽  
Binding Pocket ◽  
Bovine Insulin ◽  
Insulin Like Growth Factor ◽  
Milk Traits ◽  
Exon 2 ◽  
Ligand Binding Pocket ◽  
Cattle Breeds ◽  
Putative Ligand Binding

scholarly journals An association of C/T polymorphism in exon 2 of the bovine insulin-like growth factor 2 gene with meat production traits in Polish Holstein-Friesian cattle

2010 ◽  
Vol 55 (No. 6) ◽  
pp. 227-233 ◽  
Author(s):  
L. Zwierzchowski ◽  
E. Siadkowska ◽  
J. Oprz dek ◽  
K. Flisikowski ◽  
E. Dymnicki
Keyword(s):  
Growth Factor ◽  
Bovine Insulin ◽  
Paternal Allele ◽  
Meat Production ◽  
Insulin Like Growth Factor ◽  
Production Traits ◽  
Exon 2 ◽  
Igf2 Gene ◽  
Holstein Friesian ◽  
Friesian Cattle

The effect of the insulin-like growth factor 2 (IGF2) gene polymorphism – a g.292C>T transition in exon 2 on feed uptake and conversion, growth rates, and meat production traits in Polish Holstein-Friesian cattle was investigated. A total of 291 young bulls were genotyped using restriction fragment length polymorphism (RFLP-BsrI). Animals were slaughtered at the age of 11 or 15 months and carcass traits were examined. At the age of 11 months the association was shown of the CC genotype with higher cold carcass weight, daily gain and meat content (%) in valuable cuts. At 15 months of age the CC genotype bulls showed higher live body weight, whereas those with the CT genotype had more fat in valuable cuts. The TT genotype bulls appeared to consume more feed (dry matter and protein) and used more feed for maintenance and meat production as compared to the CC genotype. The imprinting status of the IGF2 gene was analysed using cDNA sequencing and RFLP-BsrI. In 15-months-old animals and in foetuses older than two months both IGF2 alleles, maternal and paternal, were equally expressed in liver. In a 2-months-old male foetus the IGF2 mRNA was primarily expressed from the paternal allele.  

Association of polymorphisms in exons 2 and 10 of the insulin-like growth factor 2 (IGF2) gene with milk production traits in Polish Holstein-Friesian cattle

2009 ◽  
Vol 77 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Emilia Bagnicka ◽  
Eulalia Siadkowska ◽  
Nina Strzałkowska ◽  
Beata Żelazowska ◽  
Krzysztof Flisikowski ◽  
...  
Keyword(s):  
Growth Factor ◽  
Milk Production ◽  
Insulin Like Growth Factor ◽  
Nucleotide Polymorphisms ◽  
Production Traits ◽  
Milk Production Traits ◽  
Milk Traits ◽  
Exon 2 ◽  
Holstein Friesian ◽  
Exon 10

Insulin-like growth factor 2 (IGF2) is considered to be a regulator of post-natal growth and differentiation of the mammary gland. In the present work, associations of two single nucleotide polymorphisms in the bovine IGF2 gene with milk production traits were studied in dairy Holstein-Friesian cows: the already described g.8656C>T transition in exon 2 (RFLP-BsrI) and the newly found g.24507G>T transversion in exon 10 (RFLP-HaeIII), found by sequencing 273-bp exon 10 of the IGF2 gene in six individuals. Associations were analysed individually and in combination with the multi-trait repeatability test-day animal model. The CT/GT haplotype appeared to be associated with most of the milk traits studied (differences were significant at P⩽0·001). The most frequent CT/GG haplotype seemed inferior to others in fat and protein content and daily yield of fat and protein but superior (together with the TT/GG genotype) when the daily milk yield is considered.

scholarly journals QStatin, a Selective Inhibitor of Quorum Sensing in Vibrio Species

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Byoung Sik Kim ◽  
Song Yee Jang ◽  
Ye-ji Bang ◽  
Jungwon Hwang ◽  
Youngwon Koo ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Ligand Binding ◽  
Brine Shrimp ◽  
Binding Pocket ◽  
Selective Inhibitor ◽  
Marine Environments ◽  
Marine Animals ◽  
Ligand Binding Pocket ◽  
Biochemical Analyses ◽  
Putative Ligand Binding

ABSTRACTPathogenicVibriospecies cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors ofVibriospecies have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selectiveVibrioQS inhibitor, named QStatin [1-(5-bromothiophene-2-sulfonyl)-1H-pyrazole], which affectsVibrio harveyiLuxR homologues, the well-conserved master transcriptional regulators for QS inVibriospecies. Crystallographic and biochemical analyses showed that QStatin binds tightly to a putative ligand-binding pocket in SmcR, the LuxR homologue inV. vulnificus, and changes the flexibility of the protein, thereby altering its transcription regulatory activity. Transcriptome analysis revealed that QStatin results in SmcR dysfunction, affecting the expression of SmcR regulon required for virulence, motility/chemotaxis, and biofilm dynamics. Notably, QStatin attenuated representative QS-regulated phenotypes in variousVibriospecies, including virulence against the brine shrimp (Artemia franciscana). Together, these results provide molecular insights into the mechanism of action of an effective, sustainable QS inhibitor that is less susceptible to resistance than other antimicrobial agents and useful in controlling the virulence ofVibriospecies in aquacultures.IMPORTANCEYields of aquaculture, such as penaeid shrimp hatcheries, are greatly affected by vibriosis, a disease caused by pathogenicVibrioinfections. Since bacterial cell-to-cell communication, known as quorum sensing (QS), regulates pathogenesis ofVibriospecies in marine environments, QS inhibitors have attracted attention as alternatives to conventional antibiotics in aquatic settings. Here, we used target-based high-throughput screening to identify QStatin, a potent and selective inhibitor ofV. harveyiLuxR homologues, which are well-conserved master QS regulators inVibriospecies. Structural and biochemical analyses revealed that QStatin binds tightly to a putative ligand-binding pocket on SmcR, the LuxR homologue inV. vulnificus, and affects expression of QS-regulated genes. Remarkably, QStatin attenuated diverse QS-regulated phenotypes in variousVibriospecies, including pathogenesis against brine shrimp, with no impact on bacterial viability. Taken together, the results suggest that QStatin may be a sustainable antivibriosis agent useful in aquacultures.

scholarly journals Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1151
Author(s):  
Chenyun Guo ◽  
Zhihua Wu ◽  
Weiliang Lin ◽  
Hao Xu ◽  
Ting Chang ◽  
...  
Keyword(s):  
Side Effects ◽  
Ligand Binding ◽  
Mapk Pathway ◽  
Regulatory Protein ◽  
Therapeutic Index ◽  
Binding Pocket ◽  
Biological Macromolecules ◽  
Inhibitory Protein ◽  
Ligand Binding Pocket ◽  
Raf1 Kinase

Suramin was initially used to treat African sleeping sickness and has been clinically tested to treat human cancers and HIV infection in the recent years. However, the therapeutic index is low with numerous clinical side-effects, attributed to its diverse interactions with multiple biological macromolecules. Here, we report a novel binding target of suramin, human Raf1 kinase inhibitory protein (hRKIP), which is an important regulatory protein involved in the Ras/Raf1/MEK/ERK (MAPK) signal pathway. Biolayer interference technology showed that suramin had an intermediate affinity for binding hRKIP with a dissociation constant of 23.8 µM. Both nuclear magnetic resonance technology and molecular docking analysis revealed that suramin bound to the conserved ligand-binding pocket of hRKIP, and that residues K113, W173, and Y181 play crucial roles in hRKIP binding suramin. Furthermore, suramin treatment at 160 µM could profoundly increase the ERK phosphorylation level by around 3 times. Our results indicate that suramin binds to hRKIP and prevents hRKIP from binding with hRaf1, thus promoting the MAPK pathway. This work is beneficial to both mechanistically understanding the side-effects of suramin and efficiently improving the clinical applications of suramin.

scholarly journals Ligands with poly-fluorophenyl moieties promote a local structural rearrangement in the Spinach2 and Broccoli aptamers that increases ligand affinities

2021 ◽  
Author(s):  
Sharif Anisuzzaman ◽  
Ivan M Geraskin ◽  
Muslum Ilgu ◽  
Lee Bendickson ◽  
George A Kraus ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Ligand Binding ◽  
Small Molecule ◽  
Binding Pocket ◽  
Structural Rearrangement ◽  
Structural Reorganization ◽  
Ligand Binding Pocket ◽  
Rna Remodeling ◽  
Small Molecule Ligands ◽  
Target Molecules

The interaction of nucleic acids with their molecular targets often involves structural reorganization that may traverse a complex folding landscape. With the more recent recognition that many RNAs, both coding and noncoding, may regulate cellular activities by interacting with target molecules, it becomes increasingly important to understand the means by which nucleic acids interact with their targets and how drugs might be developed that can influence critical folding transitions. We have extensively investigated the interaction of the Spinach2 and Broccoli aptamers with a library of small molecule ligands modified by various extensions from the imido nitrogen of DFHBI (3,5-difluoro-4-hydroxybenzylidene imidazolinone) that reach out from the Spinach2 ligand binding pocket. Studies of the interaction of these compounds with the aptamers revealed that poly-fluorophenyl-modified ligands initiate a slow change in aptamer affinity that takes an extended time (half-life of ~40 min) to achieve. The change in affinity appears to involve an initial disruption of the entrance to the ligand binding pocket followed by a gradual lockdown for which the most likely driving force is an interaction of the gateway adenine with a nearby 2'OH group. These results suggest that poly-fluorophenyl modifications might increase the ability of small molecule drugs to disrupt local structure and promote RNA remodeling.

Ligand binding pocket function of Drosophila USP is necessary for metamorphosis

2013 ◽  
Vol 182 ◽  
pp. 73-82 ◽  
Author(s):  
Grace Jones ◽  
Peter Teal ◽  
Vincent C. Henrich ◽  
Anna Krzywonos ◽  
Agnes Sapa ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Pocket ◽  
Ligand Binding Pocket
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