Andrea R. Matira

Bio: Andrea R. Matira is an academic researcher from Mapúa Institute of Technology. The author has contributed to research in topics: Nanomaterials & Conotoxin. The author has an hindex of 1, co-authored 3 publications receiving 3 citations. Previous affiliations of Andrea R. Matira include Chung Yuan Christian University.

Alpha-family of Conotoxins: An Analysis of Structural Determinants

Abstract: Conopeptides are small, disulfide-rich polypeptides that have great potential as sources of possible drug candidates due to their activity against membrane receptors and ion channels. A challenge to the faster high-throughput in silico screening of these potential drug candidates is their diversity in structure and relatively low sequence similarity despite similar functions. In this study, the conopeptides of the α-pharmacological family is studied based on their Cα backbone, surface topology and sequence analysis. Structural alignment using FATCAT shows good alignment of the conopeptides based on their RMSD values. The main factor contributing to the homology of their structures is not only the Cys (Cys) framework forming the disulfide bridges but also the number of intervening amino acids between the Cys residues and the length of the polypeptide. The topological landscape of the conopeptides were influenced by the Cα backbone and the nature of the intervening amino acid, and are predominantly electron-poor regions, allowing them to act as Lewis acids. This may play a role in their ability to interact with ACh receptors.

In silico Protein Structure Comparison of Conotoxins with VI/VII Cysteine Framework

Abstract: Conopeptides are small disulfide-rich peptides isolated from the venom of marine cone snails, and they are amongst the most interesting of the venom species. In this paper, in silico structural models and alignments of ω-conotoxin and different pharmacological family with the same cysteine framework (VI/VII) will be discussed using computational methods -- FATCAT and POSA. The results show that with the ω-CTX conopeptide aligned with ω-CTX conopeptide, it would most likely have significantly similar structures with lower RMSD as they both function as blockers of voltage-gated calcium channels, and this conopeptide would be ω-CTX MVIIA 1OMGA aligned with ω-CTX MVIIA 1TTK. On the other hand, having compared different pharmacological with ω-CTX would result to a fewer significantly similar results since their amino acid residues, and ion channels are quite different. Multiple alignment of structures across different pharmacological families show similarities in their polypeptide backbone. Hence,conotoxins sharing the same cysteine framework can be used as models for deducing the polypeptide backbone of a conotoxin with unknown structure.

A perspective on toxicology of Conus venom peptides

Abstract: The evolutionarily unique and ecologically diverse family Conidae presents fundamental opportunities for marine pharmacology research and drug discovery.The focus of this investigation is to summarize the worldwide distribution of Conus and their species diversity with special reference to the Indian coast.In addition,this study will contribute to understanding the structural properties of conotoxin and therapeutic application of Conus venom peptides.Cone snails can inject a mix of various conotoxins and these venoms are their major weapon for prey capture,and may also have other biological purposes,and some of these conotoxins fatal to humans.Conns venoms contain a remarkable diversity of pharmacologically active small peptides;their targets are an iron channel and receptors in the neuromuscular system.Interspecific divergence is pronounced in venom peptide genes,which is generally attributed to their species specific biotic interactions.There is a notable interspecific divergence observed in venom peptide genes,which can be justified as of biotic interactions that stipulate species peculiar habitat and ecology of cone snails.There are several conopeptides used in clinical trials and one peptide(Ziconotide) has received FDA approval for treatment of pain.This perspective provides a comprehensive overview of the distribution of cone shells and focus on the molecular approach in documenting their taxonomy and diversity with special reference to geographic distribution of Indian cone snails,structure and properties of conopeptide and their pharmacological targets and future directions.

Principal Component and Structural Element Analysis Provide Insights into the Evolutionary Divergence of Conotoxins

Abstract: Simple Summary Conotoxins are small, structured components found in the venom of predatory cone snails. They were proven to be valuable probes and models for drug discovery and protein evolution studies. Conotoxins present an opportunity to study protein divergence and discover potential human therapeutic landscapes. Although there is considerable literature on conotoxin evolution and activity, what pushed conotoxin divergence remains unclear. Hence, in this paper, we conducted a two-phase study that investigated conotoxin evolution in terms of divergence, followed by structural analysis to determine the relevant structural elements. By understanding the evolution of conotoxins, we identified patterns that account for their superior specificity. The results revealed similarities based on the cone snail’s diet preference. The structural elements are in synch with their target prey preference as if cone snails evolved to fine-tune their conopeptide armory to respond to evolutionary pressures by producing conotoxins selective for their prey of choice. We identified several structural elements that account for this specificity. Conservation patterns are observed within diet subgroups but are divergent from other groups. Abstract Predatory cone snails (Conus) developed a sophisticated neuropharmacological mechanism to capture prey, escape against other predators, and deter competitors. Their venom’s remarkable specificity for various ion channels and receptors is an evolutionary feat attributable to the venom’s variety of peptide components (conotoxins). However, what caused conotoxin divergence remains unclear and may be related to the role of prey shift. Principal component analysis revealed clustering events within diet subgroups indicating peptide sequence similarity patterns based on the prey they subdue. Molecular analyses using multiple sequence alignment and structural element analysis were conducted to observe the events at the molecular level that caused the subgrouping. Three distinct subgroups were identified. Results showed homologous regions and conserved residues within diet subgroups but divergent between other groups. We specified that these structural elements caused subgrouping in alpha conotoxins that may play a role in function specificity. In each diet subgroup, amino acid character, length of intervening amino acids between cysteine residues, and polypeptide length influenced subgrouping. This study provides molecular insights into the role of prey shift, specifically diet preference, in conotoxin divergence.