FAM72 is a novel neuronal progenitor cell (NPC) self-renewal supporting protein expressed under physiological conditions at low levels in other tissues. Accumulating data indicate the potential pivotal tumourigenic effects of FAM72. Our in silico human genome-wide analysis (GWA) revealed that the FAM72 gene family consists of four human-specific paralogous members, all of which are located on chromosome (chr) 1. Unique asymmetric FAM72 segmental gene duplications are most likely to have occurred in conjunction with the paired genomic neighbour SRGAP2 (SLIT-ROBO Rho GTPase activating protein), as both genes have four paralogues in humans but only one vertebra-emerging orthologue in all other species. No species with two or three FAM72/SRGAP2 gene pairs could be identified, and the four exclusively human-defining ohnologues, with different mutation patterns in Homo neanderthalensis and Denisova hominin, may remain under epigenetic control through long non-coding (lnc) RNAs.
Carbon (C), hydrogen (H), nitrogen (N), oxygen (O), and sulfur (S) atoms intrigue as they are the foundation for amino acid (AA) composition and the folding and functions of proteins and thus define and control the survival of a cell, the smallest unit of life. Here, we calculated the proteomic atom distribution in > 1500 randomly selected species across the entire current phylogenetic tree and identified uracil-5-methyltransferase (U5MTase) of the protozoan parasite Plasmodium falciparum (Pf, strain Pf3D7), with a distinct atom and AA distribution pattern. We determined its apicoplast location and in silico 3D protein structure to refocus attention exclusively on U5MTase with tremendous potential for therapeutic intervention in malaria. Around 300 million clinical cases of malaria occur each year in tropical and subtropical regions of the world, resulting in over one million deaths annually, placing malaria among the most serious infectious diseases. Genomic and proteomic research of the clades of parasites containing Pf is progressing slowly and the functions of most of the~5300 genes are still unknown. We applied a 'bottom-up' comparative proteomic atomics analysis across the phylogenetic tree to visualize a protein molecule on its actual basis -i. e., its atomic level. We identified a protruding Pf3D7-specific U5MTase, determined its 3D protein structure, and identified potential inhibitory drug molecules through in silico drug screening that might serve as possible remedies for the treatment of malaria. Besides, this atomic-based proteome map provides a unique approach for the identification of parasite-specific proteins that could be considered as novel therapeutic targets.
Bioactive constituents
from natural sources are of great interest
as alternatives to synthetic compounds for the treatment of various
diseases, including diabetes mellitus. In the present study, phytochemicals
present in Leucaena leucocephala (Lam.)
De Wit leaves were identified by gas chromatography–mass spectrometry
and further examined by qualitative and quantitative methods. α-Amylase
enzyme activity assays were performed and revealed that L. leucocephala (Lam.) De Wit leaf extract inhibited
enzyme activity in a dose-dependent manner, with efficacy similar
to that of the standard α-amylase inhibitor acarbose. To determine
which phytochemicals were involved in α-amylase enzyme inhibition, in silico virtual screening of the absorption, distribution,
metabolism, excretion, and toxicity properties was performed and pharmacophore
dynamics were assessed. We identified hexadecenoic acid and oleic
acid ((Z)-octadec-9-enoic acid) as α-amylase inhibitors. The
binding stability of α-amylase to those two fatty acids was
confirmed in silico by molecular docking and a molecular
dynamics simulation performed for 100 ns. Together, our findings indicate
that L. leucocephala (Lam.) De Wit-derived
hexadecanoic acid and oleic acid are natural product-based antidiabetic
compounds that can potentially be used to manage diabetes mellitus.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.