Identification of glucosyl-3-phosphoglycerate phosphatase as a novel drug target against resistant strain of Mycobacterium tuberculosis (XDR1219) by using comparative metabolic pathway approach

Uddin, Reaz; Zahra, Noor-ul-Ain; Azam, Syed Sikander

doi:10.1016/j.compbiolchem.2019.01.011

Cited by 11 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular docking analysis was performed with the identified ligand from the ProBis server and the modeled structure through AutoDock 4.2 tool. The ligand was docked followed by the parameters of 250 times Lamarckian GA settings resulting in 27,000 numbers of generations (Uddin and Azam 2019 ). The AutoDock results revealed different conformations and orientations of ligand binding at the active site of protein with diverse binding energies.…”

Section: Resultsmentioning

confidence: 99%

“…The BLASTp resulted in ‘Hits’ (Homologous sequence between the host and the pathogen) and ‘No Hits’ (Non-homologous sequences). The ‘No Hits’ proteins were selected for further steps of the study (Uddin and Azam 2019 ). The non-homologous (No Hits) sequences were selected and retrieved for further analysis to avoid the functional and structural similarities with human proteins in order to minimize the cross reactivity.…”

Section: Methodsmentioning

confidence: 99%

“…The proteins with modeled structure were used as target protein while identified compound was used as a ligand. The standard docking procedure was used for the molecular docking using AutoDock (Uddin and Azam 2019 ).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Integrated bioinformatics based subtractive genomics approach to decipher the therapeutic function of hypothetical proteins from Salmonella typhi XDR H-58 strain

Khan

Uddin

2022

Biotechnol Lett

Self Cite

View full text Add to dashboard Cite

Purpose The efficacy of drugs against Salmonella infection have compromised due to emerging XDR H58 strain. There is a dire need to find novel antimicrobial drug targets as well as drug candidates to cure by the XDR strain of Salmonella . It is observed that the complete genome sequence of the XDR H58 strain contains a large number of hypothetical proteins with unknown cellular and biological functions. Hence, it is indispensable to annotate these proteins functionally as well as structurally to identify novel drug targets. Methods In the current study, a comparative genomics and proteomics based approach was applied to find the novel drug targets in XDR strain while comparing the MDR and NR strains of Salmonella typhi . Results The characterization of ~ 350 hypothetical proteins were performed through determination of their physio-chemical properties, sub-cellular localization, functional annotation, and structure-based studies. As a result, only five proteins were prioritized as essential, druggable, and virulent proteins. Moreover, only one protein i.e. WP_000916613.1 was functionally annotated with high confidence and subjected to further structure-based analysis. Conclusion The current study presents a hypothetical protein from the XDR S . typhi proteome as a potential pharmacological target against which novel therapeutic candidates may be predicted. The outcome of the current study may lead to formulate a general set of pipelines for better understanding of the role of hypothetical proteins in pathogenesis of not only Salmonella but also for other pathogens. Supplementary Information The online version contains supplementary material available at 10.1007/s10529-021-03219-6.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Integrated bioinformatics based subtractive genomics approach to decipher the therapeutic function of hypothetical proteins from Salmonella typhi XDR H-58 strain

Khan

Uddin

2022

Biotechnol Lett

Self Cite

View full text Add to dashboard Cite

show abstract

“…All the selected compounds, myxopyronin A and rifampin were docked into the switch region of bacterial RNAP (PDB ID: 3DXJ), and the binding energy was calculated by AutoDock 4.2 (Scripps Research Institute) (Morris et al., 2009). The negative and low binding energy values indicate strong interactions between the compounds and RNAP (Uddin, Zahra, & Azam, 2019). As illustrated in Table 6, compound 6e in complex with RNAP had the lowest binding energy value of −8.92 kcal/mol, whereas compounds 2g , 2h , 2k , 6f, and 6i had binding energies of −7.15, −7.69, −8.44, −8.22, and −6.20 kcal/mol, respectively.…”

Section: Resultsmentioning

confidence: 99%

Discovery of novel N‐aryl pyrrothine derivatives as bacterial RNA polymerase inhibitors

et al. 2020

View full text Add to dashboard Cite

Bacterial RNA polymerase (RNAP) is a validated drug target for broad‐spectrum antibiotics, and its “switch region” is considered as the promising binding site for novel antibiotics. Based on the core scaffold of dithiolopyrrolone, a series of N‐aryl pyrrothine derivatives was designed, synthesized, and evaluated for their antibacterial activity. Compounds generally displayed more active against Gram‐positive bacteria, but less against Gram‐negative bacteria. Among them, compound 6e exhibited moderate antibacterial activity against clinical isolates of rifampin‐resistant Staphylococcus aureus with minimum inhibition concentration value of 1–2 μg/ml and inhibited Escherichia coli RNAP with IC50 value of 12.0 ± 0.9 μM. In addition, compound 6e showed certain degree of cytotoxicity against HepG2 and LO2 cells. Furthermore, molecular docking studies suggested that compound 6e might interact with the switch region of bacterial RNAP in a similar conformation to myxopyronin A. Together, the N‐aryl pyrrothine scaffold is a promising lead for discovery of antibacterial drugs acting against bacterial RNAP.

show abstract

“…The ligand was docked and implemented using 250 times Lamarckian GA settings, resulting in a maximum of 27,000 generations and 2,500,000 evaluations. [ 36 ]. The re-docking was performed to assess the performance of docking program for its capability of reproducing the same crystal conformation of the bound ligand [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Subtractive genomics profiling for potential drug targets identification against Moraxella catarrhalis

et al. 2022

Self Cite

View full text Add to dashboard Cite

Moraxella catarrhalis (M. catarrhalis) is a gram-negative bacterium, responsible for major respiratory tract and middle ear infection in infants and adults. The recent emergence of the antibiotic resistance M. catarrhalis demands the prioritization of an effective drug target as a top priority. Fortunately, the failure of new drugs and host toxicity associated with traditional drug development approaches can be avoided by using an in silico subtractive genomics approach. In the current study, the advanced in silico genome subtraction approach was applied to identify potential and pathogen-specific drug targets against M. catarrhalis. We applied a series of subtraction methods from the whole genome of pathogen based on certain steps i.e. paralogous protein that have extensive homology with humans, essential, drug like, non-virulent, and resistant proteins. Only 38 potent drug targets were identified in this study. Eventually, one protein was identified as a potential new drug target and forwarded to the structure-based studies i.e. histidine kinase (UniProt ID: D5VAF6). Furthermore, virtual screening of 2000 compounds from the ZINC database was performed against the histidine kinase that resulted in the shortlisting of three compounds as the potential therapeutic candidates based on their binding energies and the properties exhibited using ADMET analysis. The identified protein gives a platform for the discovery of a lead drug candidate that may inhibit it and may help to eradicate the otitis media caused by drug-resistant M. catarrhalis. Nevertheless, the current study helped in creating a pipeline for drug target identification that may assist wet-lab research in the future.

show abstract

Identification of glucosyl-3-phosphoglycerate phosphatase as a novel drug target against resistant strain of Mycobacterium tuberculosis (XDR1219) by using comparative metabolic pathway approach

Cited by 11 publications

References 40 publications

Integrated bioinformatics based subtractive genomics approach to decipher the therapeutic function of hypothetical proteins from Salmonella typhi XDR H-58 strain

Integrated bioinformatics based subtractive genomics approach to decipher the therapeutic function of hypothetical proteins from Salmonella typhi XDR H-58 strain

Discovery of novel N‐aryl pyrrothine derivatives as bacterial RNA polymerase inhibitors

Subtractive genomics profiling for potential drug targets identification against Moraxella catarrhalis

Contact Info

Product

Resources

About