The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes

The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes Publisher

Attaran B^{1, 2} ; Salehi N³ ; Ghadiri B¹ ; Esmaeili M¹ ; Kalateh S¹ ; Tashakoripour M⁴ ; Eshagh Hosseini M⁴ ; Mohammadi M¹

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1. HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran
2. Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
3. Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
4. Gastroenterology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: Gut Pathogens Published:2021

Abstract

Background: Amoxicillin-resistant H. pylori strains are increasing worldwide. To explore the potential resistance mechanisms involved, the 3D structure modeling and access tunnel prediction for penicillin-binding proteins (PBP1A) was performed, based on the Streptococcus pneumoniae, PBP 3D structure. Molecular covalent docking was used to determine the interactions between amoxicillin (AMX) and PBP1A. Results: The AMX-Ser368 covalent complex interacts with the binding site residues (Gly367, Ala369, ILE370, Lys371, Tyr416, Ser433, Thr541, Thr556, Gly557, Thr558, and Asn560) of PBP1A, non-covalently. Six tunnel-like structures, accessing the PBP1A binding site, were characterized, using the CAVER algorithm. Tunnel-1 was the ultimate access route, leading to the drug catalytic binding residue (Ser368). This tunnel comprises of eighteen amino acid residues, 8 of which are shared with the drug binding site. Subsequently, to screen the presence of PBP1A mutations, in the binding site and tunnel residues, in our clinical strains, in vitro assays were performed. H. pylori strains, isolated under gastroscopy, underwent AMX susceptibility testing by E-test. Of the 100 clinical strains tested, 4 were AMX-resistant. The transpeptidase domain of the pbp1a gene of these resistant, plus 10 randomly selected AMX-susceptible strains, were amplified and sequenced. Of the amino acids lining the tunnel-1 and binding site residues, three (Ser414Arg, Val469Met and Thr556Ser) substitutions, were detected in 2 of the 4 resistant and none of the sequenced susceptible strains, respectively. Conclusions: We hypothesize that mutations in amino acid residues lining the binding site and/or tunnel-1, resulting in conformational/spatial changes, may block drug binding to PBP1A and cause AMX resistance. © 2021, The Author(s).

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Style	Citing Format
MLA	Attaran B, et al.. "The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes." Gut Pathogens, vol. 13, no. 1, 2021, pp. -.
APA	Attaran B, Salehi N, Ghadiri B, Esmaeili M, Kalateh S, Tashakoripour M, Eshagh Hosseini M, Mohammadi M (2021). The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes. Gut Pathogens, 13(1), -.
Chicago	Attaran B, Salehi N, Ghadiri B, Esmaeili M, Kalateh S, Tashakoripour M, Eshagh Hosseini M, Mohammadi M. "The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes." Gut Pathogens 13, no. 1 (2021): -.
Harvard	Attaran B et al. (2021) 'The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes', Gut Pathogens, 13(1), pp. -.
Vancouver	Attaran B, Salehi N, Ghadiri B, Esmaeili M, Kalateh S, Tashakoripour M, et al.. The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes. Gut Pathogens. 2021;13(1):-.
BibTex	@article{ author = {Attaran B and Salehi N and Ghadiri B and Esmaeili M and Kalateh S and Tashakoripour M and Eshagh Hosseini M and Mohammadi M}, title = {The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes}, journal = {Gut Pathogens}, volume = {13}, number = {1}, pages = {-}, year = {2021} }
RIS	TY - JOUR AU - Attaran B AU - Salehi N AU - Ghadiri B AU - Esmaeili M AU - Kalateh S AU - Tashakoripour M AU - Eshagh Hosseini M AU - Mohammadi M TI - The Penicillin Binding Protein 1A of Helicobacter Pylori, Its Amoxicillin Binding Site and Access Routes JO - Gut Pathogens VL - 13 IS - 1 SP - EP - PY - 2021 ER -

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