COMPUTATIONAL MODELING AND STRUCTURAL STUDIES OF THE PROTEIN 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN PYROPHOSPHOKINASE FROM Pseudomonas aeruginosa

Abstract

Due to the high mortality rate associated with hospital infections caused by the bacterium Pseudomonas aeruginosa, it is relevant to conduct studies on bacterial proteins that may serve as therapeutic targets for the discovery of new antimicrobial drugs. Enzymes not found in the human organism, such as 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), play an important metabolic role in microorganisms and are therefore valuable potential targets (CHHABRA et al., 2012). HPPK is part of the folate biosynthetic pathway, a compound essential for the proper functioning of P. aeruginosa cells. Thus, in this work, homology-based computational modeling of P. aeruginosa HPPK (PaHPPK) was performed. Specifically, models of PaHPPK were obtained in different conformational states corresponding to each step of the pyrophosphokinase reaction, in which substrates and products were also modeled. The best-constructed structures were selected based on the lowest DOPE score (SALI & SHEN, 2006), and comparison of the models suggested a potential coupling mechanism between the adenine-binding region of ATP and the loop that covers this substrate. It is expected that these theoretical insights may complement biochemical knowledge and assist in the identification of ligands targeting HPPK as a therapeutic candidate.