Open Access3D-QSAR study of adenosine 5’-phosphosulfate (APS) analouges as ligands for APS reductase
Author(s) -
Suzana Erić,
Ilija Cvijetić,
Mire Zloh
Publication year - 2021
Publication title -
journal of the serbian chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.227
H-Index - 45
eISSN - 1820-7421
pISSN - 0352-5139
DOI - 10.2298/jsc201128015e
Subject(s) - quantitative structure–activity relationship , reductase , homology modeling , stereochemistry , chemistry , enzyme , adenosine , computational biology , mycobacterium tuberculosis , assimilation (phonology) , biochemistry , biology , tuberculosis , medicine , philosophy , pathology , linguistics
Metabolism of sulfur (sulfur assimilation pathway, SAP) is one of the key pathways for the pathogenesis and survival of persistant bacteria, such as Mycobacterium tuberculosis (Mtb), in the latent period. Adenosine 5'-phosphosulfate reductase (APSR) is an important enzyme involved in the SAP, absent from the human body, so it might represent a valid target for development of new antituberculosis drugs. This work aimed to develop 3D-QSAR model based on the crystal structure of APSR from Pseudomonas aeruginosa, which shows high degree of homology with APSR from Mtb, in complex with its substrate, adenosine 5'-phosphosulfate (APS). 3D-QSAR model was built from a set of 16 nucleotide analogues of APS using alignment-independent descriptors derived from molecular interaction fields (MIF). The model improves the understanding of the key characteristics of molecules necessary for the interaction with target, and enables the rational design of novel small molecule inhibitors of Mtb APSR.