The oxa 23 gene is present in plasmids of Acinetobacter species, making these bacteria resistant to many antibiotics.oxa 23 oxa 23 The oxa 23 gene encodes for the class D b -lactamase, which hydrolyzes carbapenems. This enzyme has become a serious clinical problem because it can reduce the effectiveness of critically important antibiotics such as carbapenems. The oxa 23 gene is also found in several other Gram-negative bacteria such as Enterobacter. The presence of this gene in Acinetobacter species has facilitated the spread of oxa 23-producing strains, and this has led to an increase in infections caused by these bacteria.
In order to better understand the functioning mechanism of this enzyme, we performed a molecular dynamics simulation of OXA-23 in complex with the antibiotic meropenem.oxa 23 The results show that the protein is able to assume different conformations. In particular, it is able to move in regions that are located above the active site of the protein. These results are important for a correct understanding of how this protein can hydrolyze various classes of carbapenems.
We calculated the root-mean-square-fluctuation (RMSF) values for each of the residues in the structure, and we determined which areas of the protein are most mobile by examining the local distribution of the RMSF values.oxa 23 The regions of the protein that are most flexible are characterized by high RMSF values. This result indicates that the protein is able to move in these regions in response to changes in abiotic conditions.
We used PCA (principal component analysis), a widely-used technique in exploratory data analysis and multivariate statistics, to perform a trajectory analysis of the protein.oxa 23 This type of analysis uses the dimensionality reduction (reduction in dimensions) algorithm to reduce a large number of variables that describe a set of data (in our case the dynamics of the protein, described by three Cartesian coordinates for each of the atoms and for every sampling time) to a smaller number of latent variables that represent the most prominent features of the dynamics. The oxa 23-meropenem molecule trajectory clearly shows that the protein visits two regions, one of which is visited more frequently than the other.
This study demonstrates that a dynamic approach can be successfully used to gain insight into the functioning mechanisms of proteins.oxa 23 The oxa 23 molecule, which is present in a wide range of Acinetobacter species and other Gram-negative bacteria such as Proteus mirabilis, can adopt multiple structures that allow it to hydrolyze several classes of antibiotics. The findings of this study could lead to the development of new antibiotics that can effectively inhibit these b -lactamases. Furthermore, the results suggest that the promiscuity of OXA-23 may be partly explained by the flexibility and rotameric properties of some of its regions. This is important not only for a more precise understanding of the mechanism of action of this enzyme, but also for designing non-hydrolysable b -lactams and specific inhibitors of this type of CHDL.