Abstract
Extended-spectrum-β-lactamases (ESBLs), constitutes the growing class of betalactamses, these are enzymes produced by bacteria which impart resistance against advanced-generation-cephalosporins. SHV enzymes are among the most prevalent ESBLs. The mode of molecular interactions of recent SHV-variants to advanced generation cephalosporins has not been reported yet. This is the first time we are reporting the insilico study of these recent variants with new generation cephaosporins. Homology models for SHV-105, SHV-95, SHV-89, SHV-61 and SHV-48 were generated using MODELLER9v3. New generation Cephalosporins were selected to target the active site amino acid residues of these modeled SHV enzymes for predicting comparative efficacies of these inhibitors against the said enzymes on the basis of interaction energies of docking. The docked complexes were analyzed by using DISCOVERY STUDIO 2.5. In this study A237, S70, K234, R275, N132, R244 and S130 were found crucial to the correct positioning of drugs within the binding site of SHV enzymes in 11, 6, 6, 6, 5, 5 and 5 instances, respectively. On the basis of interaction energy and Ki calculations cefatoxime emerged as the most efficient among the other advanced cephalosporins against all the studied SHV variants, excluding SHV-48 where ceftazidime was found to be most effective drug. Furthermore, this study identified amino acid residues crucial to 'SHV-Cephalosporins' interactions and this information will be useful in designing effective and versatile drug candidates.
Highlights
Multidrug resistance in bacteria is becoming common, both in the community and nosocomial settings [1]
Extended spectrum β-lactamases (ESBLs) are the enzymes produced by resistant bacteria which hydrolyze advanced-generation cephalosporin antibiotics and cause resistance against these drugs, SHV enzymes are among the most prevalent ESBLs [2]
Aims of the study were: (i) Modeling of recent SHV variants, (ii) Docking of advance generation cephalosporins with modeled SHV enzymes to identify amino acid residues crucial to their interaction, and (iii) predicting comparative efficacies of these drugs against the said enzymes on the basis of interaction energies of docking
Summary
Multidrug resistance in bacteria is becoming common, both in the community and nosocomial settings [1]. Identification of the amino acid residues crucial to the interaction between SHV-variants (the bacterial enzymes) and β-drug molecules is a topic of priority research. This is first study reporting modeling of SHV-105/95/89/61 or 48 and their docking with advanced generation cephalosporins .
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
