Chinese scholars analyze the function mechanism of the pathogenic bacteria cytocylic acid flipping enzyme

Science and Technology Daily, Hefei, March 24 (Reporter Wu Changfeng) reporter from the University of Science and Technology of China was informed that the university's National Research Center for Microscale Material Science and the School of Life Sciences Professor Chen Yuxing, Professor Zhou Congzhao and Professor Sun Linfeng team cooperation, expounded the Staphylococcus aphrobacteria cell squash flip enzyme transport cell sorbic acid mechanism and flip enzyme-specific inhibitor inhibitor mechanism. The findings were published online online in molecular biotechnology, a professional journal in the field of microbiology.
Staphylococcus aureus (MRSA) is one of the leading clinically pathogenic bacteria, and the infections it causes are difficult to cure and may even kill. As a result of antibiotic abuse in recent β has emerged with MRSA strains that are resistant to all drugs called steroids. The research shows that staphylococcus aphdobacteria cell wall main component cytosic acid is one of the key factors causing drug resistance. In Glacin-positive bacteria, cell wall acid is a class of anion polypolymers that are co-priced and connected to peptide polysaccharides. Cell wall acid plays an important role in bacterial division, biofilm formation, host colonization and bacterial infection. Therefore, the key enzyme in the synthesis path of cell wall acid is an important target of new antimicrobial drugs. As one of the most promising antibiotic targets, flip enzymes and their inhibitors have been widely studied. Small molecule-specific inhibitors of pilot compounds have recently been identified as inhibitors with high specific inhibition efficiency, but the molecular mechanism of inhibition is not clear.
The researchers analyzed the isotope protein of Staphylococcus aphrobacteria cell squash flip enzyme by using the frozen electroscope method, and based on the structure, the researchers calculated the substrate transport channel, and expounded the substrate specificity recognition mechanism by analyzing the amino acid residue properties of the composition channel and combining it with physiological experiments. The molecular mechanism of flipping enzymes and their isology proteins to achieve substrate transport by using the principle of "crank link" is proposed by structural ratio study. ABC transport proteins with similar structural characteristics can use this mechanism to transport larger substrates through relatively small overall compositional changes.
the study further determined the exact location of specific inhibitors binding to flip enzymes through bio-chemical experiments and computer simulations, and clarified the molecular mechanism of inhibiting the transport of cytocytosic acid by flipping enzymes. The results will provide structural basis and theoretical guidance for designing and optimizing new antibiotics for MRSA.