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Proteomic Atomics Reveals a Distinctive Uracil‐5‐Methyltransferase
Author(s) -
Pramanik Subrata,
Thaker Manisha,
Perumal Ananda Gopu,
Ekambaram Rajasekaran,
Poondla Naresh,
Schmidt Markus,
Kim PokSon,
Kutzner Arne,
Heese Klaus
Publication year - 2020
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201900135
Subject(s) - apicoplast , in silico , biology , phylogenetic tree , proteome , computational biology , malaria , plasmodium falciparum , evolutionary biology , genetics , gene , plastid , chloroplast , immunology
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 Pf 3D7), 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 Pf 3D7‐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.