A new era for TUJNS: quality, transparency, and visibility through professional publishing

Background:The FabI enzyme, crucial for fatty acid synthesis, represents a promising target for antimalarial drug development, particularly in Plasmodium falciparum.Aims: To comprehensively characterize the P. falciparum FabI enzyme by elucidating its evolutionary relationships, physicochemical properties, and detailed structural features using advanced in silico methodologies.Methods: An extensive computational analysis was performed on 25 FabI protein sequences, encompassing those from P. falciparum as well as diverse protozoan and bacterial species. Results:The predicted physicochemical properties indicated that P. falciparum FabI is compartively larger, more hydrophilic, and exhibits a higher isoelectric point than its bacterial homologs.Sequence alignment and phylogenetic reconstruction revealed a clear evolutionary divergence of P. falciparum FabI from bacterial orthologs, supporting its origin through an ancient horizontal gene transfer event and its localization to the apicoplast.Further sequence analysis identified two conserved motifs mapped to a central NAD(P) binding Rossmann-fold domain, which is essential for the enzyme's catalytic function.The predicted three-dimensional (3D) structure of P. falciparum FabI exhibited a characteristic /-fold architecture forming a dimeric complex.A persistent challenge was noted in the N-terminal region, predicted to be a flexible, cleavable signal/transit peptide, accounting for its lower structural confidence.PDBsum analysis delineated its structural organization, consisting of 19 -helices and 9 -strands, with a notable absence of disulfide bridges.Additionally, proteolytic digestion produced multiple cleavage patterns.CASTp 3.0 analysis revelaed a complex active site comprising several sub-pockets and key functional residues, along with buried cavities. zetDayanak: Ya asidi sentezi iin ok nemli olan FabI enzimi, zellikle Plasmodium falciparum'da stma ilac gelitirme iin umut verici bir hedef oluturmaktadr