scholarly journals Kākāpō reproduction: Identification of steroid receptors and oestrogenic activity in native flora

2021 ◽  
Author(s):  
◽  
Catherine Elizabeth Judith Davis
Keyword(s):  
New Zealand ◽  
Amino Acid ◽  
In Silico ◽  
Oestrogen Receptor ◽  
Steroid Receptors ◽  
Avian Species ◽  
Reproductive Pattern ◽  
Parrot Species ◽  
In Silico Modelling ◽  
Binding Position

<p>Kākāpō (Strigops habroptilus) are a critically endangered parrot species endemic to New Zealand that exhibit a reproductive strategy linked to “masting” years. Crucial to their survival is increased reproductive success. It has been hypothesised that their pattern of reproduction is synchronised with a steroidal “trigger” present in plants during intensive masting. If this hypothesis is valid, then Kākāpō and other closely related NZ parrots might be receptive to these masting plants in a manner different from that of other avian species.  The aims of this study were firstly, to identify whether unique amino acid motifs were present in the ligand binding domains (LBD) for the steroid receptors oestrogen receptor α (ER-α), oestrogen receptor β (ER-β), androgen receptor (AR) and progesterone receptor (PR) for the New Zealand parrots Kākāpō, Kākā, Kākāriki and Kea. These LBD amino acid sequences were compared with those in an Australian parrot, the Cockatiel, as well as in Chicken and Japanese Quail. Moreover, the role of these amino acid changes on the binding of ligands (both the native ligand and other steroidogenic compounds) for ER-α was assessed by in silico modelling by comparing the most favourable binding position of the ligands in the three-dimensional structure of Kākāpō ER-α with that of human ER-α. The second aim was to test extracts of New Zealand native plants known to be a food source for Kākāpō for their seasonal variation in oestrogenic activity and hence possible involvement in the reproductive cycle of Kākāpō.  The LBD for ER-β and AR of the parrot species (New Zealand and Australian) displayed 100% identity whilst those for ER-α and PR had variations. When the parrot sequences were compared with those for other avian species and human, there were a number of amino acid differences present, with the greatest disparity present in the LBD of ER-α. From in silico modelling studies, the amino acid substitutions in this receptor were predicted to have an indirect influence on the binding position of both 17β-oestradiol and a number of phytoestrogens through changes in the structure of this region. Consequently, this could have an effect on the binding affinity of certain plant chemicals for ER-α and thus their potency.  Plants extracts from the foliage and fruit of native New Zealand species were screened for oestrogenic activity in a yeast bioassay transfected with the human isoform of ER-α. The results from these experiments indicated that all the plants tested (excluding Dacrycarpus dacrydioides) exhibited detectable oestrogenic activity and a number also displayed variable and sometimes seasonal trends in activity.  In summary, the results in this study identified ER-α LBD amino acid motifs unique to New Zealand parrots. For the other steroid receptors, the ER-β LBD had a three amino acid combination of M, V and L that was only present in the parrot species whilst both the AR and PR LBD displayed much greater inter-species conservation. These changes, particularly those in the ER-α LBD, may influence the binding of steroidogenic compounds, known to be present in the plants consumed by Kākāpō as demonstrated by in silico modelling. Thus, this research provides evidence that the diet of Kākāpō may influence their reproductive pattern. However, it remains to be determined whether the steroidogenic potency of these plant extracts is modified when interacting with the unique LBD of native NZ parrots.</p>

scholarly journals Kākāpō reproduction: Identification of steroid receptors and oestrogenic activity in native flora

2021 ◽  
Author(s):  
◽  
Catherine Elizabeth Judith Davis
Keyword(s):  
New Zealand ◽  
Amino Acid ◽  
In Silico ◽  
Oestrogen Receptor ◽  
Steroid Receptors ◽  
Avian Species ◽  
Reproductive Pattern ◽  
Parrot Species ◽  
In Silico Modelling ◽  
Binding Position

<p>Kākāpō (Strigops habroptilus) are a critically endangered parrot species endemic to New Zealand that exhibit a reproductive strategy linked to “masting” years. Crucial to their survival is increased reproductive success. It has been hypothesised that their pattern of reproduction is synchronised with a steroidal “trigger” present in plants during intensive masting. If this hypothesis is valid, then Kākāpō and other closely related NZ parrots might be receptive to these masting plants in a manner different from that of other avian species.  The aims of this study were firstly, to identify whether unique amino acid motifs were present in the ligand binding domains (LBD) for the steroid receptors oestrogen receptor α (ER-α), oestrogen receptor β (ER-β), androgen receptor (AR) and progesterone receptor (PR) for the New Zealand parrots Kākāpō, Kākā, Kākāriki and Kea. These LBD amino acid sequences were compared with those in an Australian parrot, the Cockatiel, as well as in Chicken and Japanese Quail. Moreover, the role of these amino acid changes on the binding of ligands (both the native ligand and other steroidogenic compounds) for ER-α was assessed by in silico modelling by comparing the most favourable binding position of the ligands in the three-dimensional structure of Kākāpō ER-α with that of human ER-α. The second aim was to test extracts of New Zealand native plants known to be a food source for Kākāpō for their seasonal variation in oestrogenic activity and hence possible involvement in the reproductive cycle of Kākāpō.  The LBD for ER-β and AR of the parrot species (New Zealand and Australian) displayed 100% identity whilst those for ER-α and PR had variations. When the parrot sequences were compared with those for other avian species and human, there were a number of amino acid differences present, with the greatest disparity present in the LBD of ER-α. From in silico modelling studies, the amino acid substitutions in this receptor were predicted to have an indirect influence on the binding position of both 17β-oestradiol and a number of phytoestrogens through changes in the structure of this region. Consequently, this could have an effect on the binding affinity of certain plant chemicals for ER-α and thus their potency.  Plants extracts from the foliage and fruit of native New Zealand species were screened for oestrogenic activity in a yeast bioassay transfected with the human isoform of ER-α. The results from these experiments indicated that all the plants tested (excluding Dacrycarpus dacrydioides) exhibited detectable oestrogenic activity and a number also displayed variable and sometimes seasonal trends in activity.  In summary, the results in this study identified ER-α LBD amino acid motifs unique to New Zealand parrots. For the other steroid receptors, the ER-β LBD had a three amino acid combination of M, V and L that was only present in the parrot species whilst both the AR and PR LBD displayed much greater inter-species conservation. These changes, particularly those in the ER-α LBD, may influence the binding of steroidogenic compounds, known to be present in the plants consumed by Kākāpō as demonstrated by in silico modelling. Thus, this research provides evidence that the diet of Kākāpō may influence their reproductive pattern. However, it remains to be determined whether the steroidogenic potency of these plant extracts is modified when interacting with the unique LBD of native NZ parrots.</p>

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using in silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs. 

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using In silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Bioinformatic Tools ◽  
Wide Range ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range ofhosts including humans and rodents. There are two copies ofmitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise ofpresented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series ofpublicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localizedandcontain both a nuclear localization signal (NLS) anda Leucine-rich nuclear export signal (NES). The activation motifs ofTDYand TSH werefound to befully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection ofa multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising ofdifferent amino acids present in MAPK1 and MAPK2 respectively, with respect to rodent and human Plasmodia. 1t is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs.

Amino Acids Sequence-based Analysis of Arginine Deiminase from Different Prokaryotic Organisms: An In Silico Approach

2020 ◽  
Vol 14 (3) ◽  
pp. 235-246
Author(s):  
Sara Abdollahi ◽  
Mohammad H. Morowvat ◽  
Amir Savardashtaki ◽  
Cambyz Irajie ◽  
Sohrab Najafipour ◽  
...  
Keyword(s):  
Amino Acid ◽  
Physicochemical Properties ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
In Silico ◽  
Bacterial Species ◽  
Arginine Deiminase ◽  
Antitumor Effects ◽  
Multiple Sequence ◽  
In Silico Studies

Background: Arginine deiminase is a bacterial enzyme, which degrades L-arginine. Some human cancers such as hepatocellular carcinoma (HCC) and melanoma are auxotrophic for arginine. Therefore, PEGylated arginine deiminase (ADI-PEG20) is a good anticancer candidate with antitumor effects. It causes local depletion of L-arginine and growth inhibition in arginineauxotrophic tumor cells. The FDA and EMA have granted orphan status to this drug. Some recently published patents have dealt with this enzyme or its PEGylated form. Objective: Due to increasing attention to it, we aimed to evaluate and compare 30 arginine deiminase proteins from different bacterial species through in silico analysis. Methods: The exploited analyses included the investigation of physicochemical properties, multiple sequence alignment (MSA), motif, superfamily, phylogenetic and 3D comparative analyses of arginine deiminase proteins thorough various bioinformatics tools. Results: The most abundant amino acid in the arginine deiminase proteins is leucine (10.13%) while the least amino acid ratio is cysteine (0.98%). Multiple sequence alignment showed 47 conserved patterns between 30 arginine deiminase amino acid sequences. The results of sequence homology among 30 different groups of arginine deiminase enzymes revealed that all the studied sequences located in amidinotransferase superfamily. Based on the phylogenetic analysis, two major clusters were identified. Considering the results of various in silico studies; we selected the five best candidates for further investigations. The 3D structures of the best five arginine deiminase proteins were generated by the I-TASSER server and PyMOL. The RAMPAGE analysis revealed that 81.4%-91.4%, of the selected sequences, were located in the favored region of arginine deiminase proteins. Conclusion: The results of this study shed light on the basic physicochemical properties of thirty major arginine deiminase sequences. The obtained data could be employed for further in vivo and clinical studies and also for developing the related therapeutic enzymes.

scholarly journals Mitigating the Adverse Effects of Polychlorinated Biphenyl Derivatives on Estrogenic Activity via Molecular Modification Techniques

2021 ◽  
Vol 18 (9) ◽  
pp. 4999
Author(s):  
Wei He ◽  
Wenhui Zhang ◽  
Zhenhua Chu ◽  
Yu Li
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Hydrophobic Interaction ◽  
Oestrogen Receptor ◽  
Polychlorinated Biphenyl ◽  
Hydrophobic Interactions ◽  
Estrogenic Activity ◽  
Average Distance ◽  
Amino Acid Residues ◽  
Hydrophobic Amino Acid

The aim of this paper is to explore the mechanism of the change in oestrogenic activity of PCBs molecules before and after modification by designing new PCBs derivatives in combination with molecular docking techniques through the constructed model of oestrogenic activity of PCBs molecules. We found that the weakened hydrophobic interaction between the hydrophobic amino acid residues and hydrophobic substituents at the binding site of PCB derivatives and human oestrogen receptor alpha (hERα) was the main reason for the weakened binding force and reduced anti-oestrogenic activity. It was consistent with the information that the hydrophobic field displayed by the 3D contour maps in the constructed oestrogen activity CoMSIA model was one of the main influencing force fields. The hydrophobic interaction between PCB derivatives and oestrogen-active receptors was negatively correlated with the average distance between hydrophobic substituents and hydrophobic amino acid residues at the hERα-binding site, and positively correlated with the number of hydrophobic amino acid residues. In other words, the smaller the average distance between the hydrophobic amino acid residues at the binding sites between the two and the more the number of them, and the stronger the oestrogen activity expression degree of PCBS derivative molecules. Therefore, hydrophobic interactions between PCB derivatives and the oestrogen receptor can be reduced by altering the microenvironmental conditions in humans. This reduces the ability of PCB derivatives to bind to the oestrogen receptor and can effectively modulate the risk of residual PCB derivatives to produce oestrogenic activity in humans.

scholarly journals In-silico modelling of fullerene and fullerene adsorbed by nO2 molecules (n(O2)@Cm with n = 1, 2, 4 and m = 48 and 60) as potential SARS-CoV-2 inhibitors

2021 ◽  
Vol 44 (3) ◽  
Author(s):  
Meziane Brahimi ◽  
Djamila SELLAM ◽  
Afaf Bouchoucha ◽  
Yassamina Arbia ◽  
Hadjer Merazka ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Modelling

scholarly journals In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2–Spike RBD Interface

2021 ◽  
Vol 22 (4) ◽  
pp. 1695
Author(s):  
Bruno O. Villoutreix ◽  
Vincent Calvez ◽  
Anne-Geneviève Marcelin ◽  
Abdel-Majid Khatib
Keyword(s):  
Amino Acid ◽  
South African ◽  
In Silico ◽  
Neutralizing Antibodies ◽  
Viral Escape ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
The South ◽  
African Strain ◽  
The Uk

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain.

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