Next Article in Journal
The Class A β-Lactamase Produced by Burkholderia Species Compromises the Potency of Tebipenem against a Panel of Isolates from the United States
Next Article in Special Issue
Computational Development of Inhibitors of Plasmid-Borne Bacterial Dihydrofolate Reductase
Previous Article in Journal
Synergism between the Synthetic Antibacterial and Antibiofilm Peptide (SAAP)-148 and Halicin
Previous Article in Special Issue
The Role of Staphylococcus aureus YycFG in Gene Regulation, Biofilm Organization and Drug Resistance
Article

An Evolutionary Conservation and Druggability Analysis of Enzymes Belonging to the Bacterial Shikimate Pathway

The Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
Academic Editor: Carlos M. Franco
Antibiotics 2022, 11(5), 675; https://doi.org/10.3390/antibiotics11050675
Received: 20 April 2022 / Revised: 11 May 2022 / Accepted: 13 May 2022 / Published: 17 May 2022
(This article belongs to the Special Issue Design and Preparation of Antimicrobial Agents)
Enzymes belonging to the shikimate pathway have long been considered promising targets for antibacterial drugs because they have no counterpart in mammals and are essential for bacterial growth and virulence. However, despite decades of research, there are currently no clinically relevant antibacterial drugs targeting any of these enzymes, and there are legitimate concerns about whether they are sufficiently druggable, i.e., whether they can be adequately modulated by small and potent drug-like molecules. In the present work, in silico analyses combining evolutionary conservation and druggability are performed to determine whether these enzymes are candidates for broad-spectrum antibacterial therapy. The results presented here indicate that the substrate-binding sites of most enzymes in this pathway are suitable drug targets because of their reasonable conservation and druggability scores. An exception was the substrate-binding site of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase, which was found to be undruggable because of its high content of charged residues and extremely high overall polarity. Although the presented study was designed from the perspective of broad-spectrum antibacterial drug development, this workflow can be readily applied to any antimicrobial target analysis, whether narrow- or broad-spectrum. Moreover, this research also contributes to a deeper understanding of these enzymes and provides valuable insights into their properties. View Full-Text
Keywords: shikimate pathway; druggability; ligandability; antibacterial; inhibitors; broad-spectrum shikimate pathway; druggability; ligandability; antibacterial; inhibitors; broad-spectrum
Show Figures

Figure 1

MDPI and ACS Style

Frlan, R. An Evolutionary Conservation and Druggability Analysis of Enzymes Belonging to the Bacterial Shikimate Pathway. Antibiotics 2022, 11, 675. https://doi.org/10.3390/antibiotics11050675

AMA Style

Frlan R. An Evolutionary Conservation and Druggability Analysis of Enzymes Belonging to the Bacterial Shikimate Pathway. Antibiotics. 2022; 11(5):675. https://doi.org/10.3390/antibiotics11050675

Chicago/Turabian Style

Frlan, Rok. 2022. "An Evolutionary Conservation and Druggability Analysis of Enzymes Belonging to the Bacterial Shikimate Pathway" Antibiotics 11, no. 5: 675. https://doi.org/10.3390/antibiotics11050675

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop