In this table are reported for each protein the interactions of the representative pose(s) reported in Table ?Table2.2. the rational design of future new compounds. Table 1 List of the structures of serine -lactamases selected for this study PBPs , and no significant differences are predicted between the wild type and mutant forms of TEM-1. The predicted binding scores of ceftriaxone, instead, tend to be lower in the case of TEM-1 with respect to PBPs . Although the difference is not fully significant in absolute values, this tendency is conserved across the various PBP with respect to all TEM-1. Thus, the interaction of -lactamases with this control drug seems to be more favored for ceftriaxone with respect to the 7-ACA derivative, suggesting that the new compound could be more resistant to -lactamases. Table 2 Results of covalent docking between 7-ACA derivative, ceftriaxone and -lactamase TEM-1 Gemifloxacin (mesylate) from  show that the predicted binding score of both the 7-ACA derivative and ceftriaxone for PC-1 is in line with that predicted for PBP4, but higher than the one predicted for PBP3. Therefore, in this case it seems that both antimicrobial molecules are more reactive towards their natural target proteins than being themselves a target for the -lactamases. Table 3 Results of covalent docking between 7-ACA derivative, ceftriaxone and other selected class A -lactamases species), which are leading cause of nosocomial infections throughout the world. These pathogens can be commonly found in the human microbiota and in the environment, and under the selective pressure provoked by the use (and misuse/abuse) of antibiotics, they were particularly able to accumulate multiple different antimicrobial resistance mechanisms carried by bacterial chromosomes, plasmids or genetic transposable elements. In this way, they are now able to escape the most common antimicrobial treatments and, particularly in healthcare settings due to the high concentration of infected people, they can be transmitted among individuals or they can colonize immunocompromised patients, becoming one of the principal causes of death of hospitalised patients . TEM-1 was the first -lactamase identified in . The proteins of this family are encoded generally by plasmidic genes and are commonly detected in based infections. TEM-1 belongs to Ambler class A and to group 2b according to Bush-Jacoby-Medeiros classification [23, 24] and is active against both penicillins and cephalosporins. The crystal structure of wild type TEM-1 -lactamase selected for the present work has been determined at 1.9?? resolution in 1995 Gemifloxacin (mesylate) . Similarly to other known -lactamases of the same class, it consists of two domains, with the active site located at the interface between them. In addition to the wild type, in order to improve our knowledge about the binding of 7-ACA derivative with this family of enzymes, we also simulated the interaction of our cephalosporin derivative with Gemifloxacin (mesylate) some mutants whose 3D structure is available. In particular, we selected the structure of the double Mouse monoclonal to A1BG mutant p.Val84Ile?+?p.Ala184Val, considered as a high resolution wild type enzyme ; of TEM-1 p.Asn132Ala, a mutant that shows a dramatic change in stability when bound to inhibitors such as moxalactam and imipenem ; of p.Met182Thr, which is isofunctional but more stable and diffracts to a higher resolution with respect to the wild type TEM-1 ; finally, of p.Glu166Asn, a deacylation-defective mutant of this -lactamase . The PC-1 -lactamase used in this study derives from the Gram positive organism belonging to the ESKAPE group . It is classified by Ambler as a class A serine penicillinase and is more specific for penicillins, being classified in the group 2a according to Bush, Jacoby and Medeiros. The structure selected for the present work has been determined at 2.0??  and, similarly to TEM-1, it consists of two closely associated domains with the active cleft located between them. SHV-1 is another -lactamase belonging to class A and group 2b, sharing approximately 68% sequence identity with TEM-1 . It can be considered another common -lactamase, found primarily in (another.