Virtual Evaluation of amino acids in of beta-lactamase SHV-1 active site and their reaction with penicillin G antibiotic

Virtual Evaluation of amino acids in of beta-lactamase SHV-1 active site and their reaction with penicillin G antibiotic
zahra baseri,^1,* Mojtaba Mortazavi,² Amir Savardashtaki,³ Kambiz Iraji,⁴ Masoud Torkzadeh,⁵
2. Department of Biotechnology, Institute of Science and High Technology and Environmental Science, Graduate University of Advanced Technology, Kerman, Iran
3. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies Shiraz University of Medical Sciences Shiraz Iran
4. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies Shiraz University of Medical Sciences Shiraz Iran
5. Department of Biotechnology, Institute of Science and High Technology and Environmental Science, Graduate University of Advanced Technology, Kerman, Iran
Introduction: Klebsiella pneumonia is known for as producing extended-spectrum beta-lactamase (ESBL) belonging to three families (TEM, SHV and CTX-M). Numerous studies have shown the high prevalence of integrons in ESBL-producing Klebsiella and their pivotal role in transmitting broad-spectrum resistance. They cause several types of infections in humans, including respiratory infections, urinary tract infections (UTIs), and bloodstream infections. Due to limited treatment options UTIs caused by antibiotic-resistant gram-negative bacteria are a growing concern. Resistance to β-lactam antibiotics is achieved by the hydrolysis of the β-lactam ring by β-lactamases. Resistance to some β-lactamses are inherent because the enzyme is encoded in the core genome of Kelebsiella pneumonia. SHV is constantly found on chromosomes and offers resistance to extended-spectrum of beta-lactame antibiotics such as ampicillin, tigecycline and piperacillin. The aim of this study was to investigate the active site amino acids of beta-lactamase enzyme involved in beta-lactam resistance.
Methods: The 3D structure of SHV-1 beta-lactamase enzyme was obtained from the protein data bank database (http://www.rcsb.org/pdb/home/home). Using molecular docking and AutoDock Vina software, the binding and reaction of the enzyme with the antibiotic penicillin G (CID: 590) was investigated.
Results: Molecular docking indicates the molecular basis of drug sensitivity. The most stable binding state of penicillin G to beta-lactamase had the lowest amount of free energy (-7.2 kcal/mol) which interacted with amino acid residues ASN170, ASN132, TYR105, VAL216 in active site of beta-lactamase.
Conclusion: With the advent of antibiotic resistance, it makes sense to look at the mechanisms of resistance because it can help decide which drugs are prescribed in different scenarios and ways to overcome them.
Keywords: Extended-spectrum beta-lactamase (ESBL), Molecular docking, Antibiotic resistance