Estudo Químico-Teórico da reação de síntese da Corismato Sintase

Abstract

Tuberculosis is an ancient infectious disease caused by Mycobacterium tuberculosis. With 9.2 million cases worldwide each year by 2008, According to WHO and the gradual loss of effectiveness of existing drugs through the resistance of microorganisms, deserves special attention from our country's authorities and encourages research in discovering new drugs that may be successful in treating this disease. For this, a widely used approach is to search for the pathogens metabolism inhibitors. The shikimic acid pathway is a biosynthetic pathway critical to maintaining the bacteria, and thus the enzymes belonging to the shikimate pathway are a prime target in the design of new antibacterial agents. The enzyme chorismate synthase catalyzes the seventh and final step of this route, converting the 5-enolpyruvylshikimate-3-phosphate (EPSP) in chorismate, this is an important precursor in other metabolic pathways, such as aromatic amino acids, folate, ubiquinone, vitamin K and other products. Understanding the chorismate synthesis reaction is controversial because there is no unanimity regarding the mechanism or the role of amino acids involved. The elucidation of it will bring a significant scientific advance, helping to understand the complexity involved in this biochemical step, and also contribute to the development of new enzyme inhibitors. The study of the synthesis reaction in question was developed employing the use of quantum chemistry computational in DFT level using the functional B3LYP and 6-31 + G (d, p) basis set. From the orbital Homo-Lumo orbitals and optimization of transition state between reactant and reaction product (QST2), it was possible to clarify some important points about the reaction . It was possible to propose a reaction mechanism in the light of this theoretical chemical study .