Analysis of Siderophore Acyltransferase SidL protein of Aspergillus fumigatus

Background: Aspergillus fumigatus is a leading opportunistic filamentous fungal pathogen whose capacity to secrete hydroxamate siderophores is central to iron acquisition, the oxidative stress response and virulence. One of the key enzymes, SidL is required for the biosynthesis of ferricrocin and hydroxyferricrocin but has never been structurally characterized. In the present study, various silico analyses were conducted to elucidate physicochemical properties, subcellular localization, secondary structure, homology model validation and protein-protein interaction network of SidL. Methods: Uniprot was used to obtain the monoacid sequence, and Expasy's ProtParam tool was used to predict physicochemical properties. The DeepLoc-2.0 was used for protein's subcellular location, InterProScan for function prediction, and PSIPRED and SOPMA for the secondary structure. SWISS-MODEL was utilized to predict the three-dimensional structure, the STRING database for protein-protein interactions, and finally, the DoGSiteScorer and FTSite for checking the Draggability and Binding Site. Results: ProtParam showed that the protein is hydrophobic and unstable with 484 amino acids, predicted molecular weight of ~54.8 kDa. Its subcellular localization was predicted as cytoplasmic, and secondary structure analysis showed it to be rich in α-helices. 3D structural model was generated by homology modeling using SWISS-MODEL and validated by SAVES quality assessment. The string analyses showed potential functional interactions with other siderophore biosynthesis enzymes and doGSiteScorer and FTSite identified a draggable binding pocket that received promising scores. Conclusions: This study presents the first comprehensive computational characterization of SidL, a siderophore acyltransferase from Aspergillus fumigatus. By highlighting SidL’s potential draggability, this work supports its consideration as a promising antifungal target, especially considering rising antifungal resistance and the urgent need for new therapeutic strategies.