Reaching toward underexplored targets in antibacterial drug design

Jukič, Marko; Gobec, Stanislav; Sova, Matej

doi:10.1002/ddr.21465

Cited by 29 publications

(27 citation statements)

References 48 publications

(72 reference statements)

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“…MurF catalyzes the last step of the cytoplasmic phase of peptidoglycan biosynthesis which is crucial to bacterial cell wall synthesis . This is an ATP‐dependent reaction utilizing d ‐ala‐ d ‐ala and UDP‐ N ‐acetyl‐muramoyl‐Ala‐ d ‐Glu‐ l ‐Lys to form UDP‐ N ‐acetyl‐ d ‐muramoyl‐ l ‐Ala‐ d ‐Glu‐ l ‐Lys‐ d ‐Ala‐ d ‐Ala (UDP‐ N ‐acetylmuramate‐pentapeptide) . Only one inhibitor, fosfomycin, has been clinically used as an effective antibiotic MurA inhibitor.…”

Section: Resultsmentioning

confidence: 99%

“…UDP‐ N ‐acetylmuramate—alanine ligase (MurC) facilitates the first ATP‐dependent peptide addition to UDP‐ N ‐acetylmuramate starting the peptide chain of UDP‐ N ‐acetylmuramate‐pentapeptide . Similar to MurF, several inhibitors of the MurC have been reported; however, little show effective antibacterial activity aside from inhibitors with an N ‐acylhydrazone scaffold that had dual inhibitory activity with MurC and MurD …”

Section: Resultsmentioning

confidence: 99%

“…53 This is an ATP-dependent reaction utilizing D-ala-D-ala and UDP-N-acetyl-muramoyl-Ala-D-Glu-L-Lys to form UDP-N-acetyl-D-muramoyl-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala (UDP-N-acetylmuramate-pentapeptide). 52,54 Only one inhibitor, fosfomycin, has been clinically used as an effective antibiotic MurA inhibitor. While there have been many reported inhibitors of MurF, many do not show antibacterial activity even with cell permeabilizers.…”

Section: Cell Wall and Lipid Synthesis And Membrane Proteinsmentioning

confidence: 99%

“…55,56 UDP-N-acetylmuramate-alanine ligase (MurC) facilitates the first ATP-dependent peptide addition to UDP-N-acetylmuramate starting the peptide chain of UDP-N-acetylmuramate-pentapeptide. 54 Similar to MurF, several inhibitors of the MurC have been reported; however, little show effective antibacterial activity aside from inhibitors with an N-acylhydrazone scaffold that had dual inhibitory activity with MurC and MurD. 55,57 2-Dehydro-3-deoxyphosphooctonate aldolase catalyzes the formation of 3-deoxy-D-manno-octulosonate 8-phosphate (Kdo8P) from phosphoenolpyruvate (PEP) and D-arabinose-5-phosphate.…”

Section: Cell Wall and Lipid Synthesis And Membrane Proteinsmentioning

confidence: 99%

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Toward a structome of Acinetobacter baumannii drug targets

et al. 2020

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Acinetobacter baumannii is well known for causing hospital‐associated infections due in part to its intrinsic antibiotic resistance as well as its ability to remain viable on surfaces and resist cleaning agents. In a previous publication, A. baumannii strain AB5075 was studied by transposon mutagenesis and 438 essential gene candidates for growth on rich‐medium were identified. The Seattle Structural Genomics Center for Infectious Disease entered 342 of these candidate essential genes into our pipeline for structure determination, in which 306 were successfully cloned into expression vectors, 192 were detectably expressed, 165 screened as soluble, 121 were purified, 52 crystalized, 30 provided diffraction data, and 29 structures were deposited in the Protein Data Bank. Here, we report these structures, compare them with human orthologs where applicable, and discuss their potential as drug targets for antibiotic development against A. baumannii.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Cell Wall and Lipid Synthesis And Membrane Proteinsmentioning

confidence: 99%

Section: Cell Wall and Lipid Synthesis And Membrane Proteinsmentioning

confidence: 99%

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Toward a structome of Acinetobacter baumannii drug targets

et al. 2020

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“…Previously, an in silico study stated that metabolic pathway proteins of Ott may act as probable target for drug discovery process (Sharma et al, 2018b). It is a well-established fact that Mur enzymes are involved in biosynthesis of bacterial cell wall using divalent metal ions as cofactor and are best intracellular therapeutic targets (Munshi et al, 2013; Moraes et al, 2015; Jukič et al, 2019). DDI enzyme uses Mg 2+ ion as cofactor and catalyzes early steps of peptidoglycan synthesis, i.e., formation of D-Ala-D-Ala and D-Ala-D-Ser dipeptides in bacteria (Tytgat et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

Bioinformatic Exploration of Metal-Binding Proteome of Zoonotic Pathogen Orientia tsutsugamushi

Sharma

Singh

et al. 2019

Front. Genet.

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Metal ions are involved in many essential biological processes and are crucial for the survival of all organisms. Identification of metal-binding proteins (MBPs) of human affecting pathogens may provide the blueprint for understanding biological metal usage and their putative roles in pathogenesis. This study is focused on the analysis of MBPs from Orientia tsutsugamushi (Ott), a causal agent of scrub typhus in humans. A total of 321 proteins were predicted as putative MBPs, based on sequence search and three-dimensional structure analysis. Majority of proteins could bind with magnesium, and the order of metal binding was Mg > Ca > Zn > Mn > Fe > Cd > Ni > Co > Cu, respectively. The predicted MBPs were functionally classified into nine broad classes. Among them, gene expression and regulation, metabolism, cell signaling, and transport classes were dominant. It was noted that the putative MBPs were localized in all subcellular compartments of Ott, but majorly found in the cytoplasm. Additionally, it was revealed that out of 321 predicted MBPs 245 proteins were putative bacterial toxins and among them, 98 proteins were nonhomologous to human proteome. Sixty putative MBPs showed the ability to interact with drug or drug-like molecules, which indicate that they may be used as broad-spectrum drug targets. These predicted MBPs from Ott could play vital role(s) in various cellular activities and virulence, hence may serve as plausible therapeutic targets to design metal-based drugs to curtail its infection.

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Preparation and characterization of zein/gelatin electrospun film loaded with ε‐polylysine and gallic acid as tuna packaging system

Li,

Zhou,

et al. 2023

J Sci Food Agric

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BACKGROUNDIn order to develop effective active packaging films for tuna preservation, zein/gelatin (ZG) composite nanofiber films loaded with ε‐polylysine (PL) and gallic acid (GA) were first prepared by electrospun method. The morphology, structure, thermal stability, hydrophobicity, antibacterial and antioxidant properties of the films and application in tuna during 4°C storages were investigated.RESULTSPL reduced the average diameter of ZG fibers, while GA increased it. PL/GA/ZG film possessed well‐distributed fiber morphology with an average diameter of 810 ± 150 nm. Fourier transform infrared spectroscopy and X‐ray diffraction results showed the physical loading of PL and GA in ZG film with unchanged main chemical bonds and crystal structure. Both the addition of PL and GA reduced hydrophobicity of the ZG film, while the PL/GA/ZG film is still hydrophobic. GA enhanced thermal stability and contributed to antioxidant activity of PL/GA/ZG film. PL and GA synergetic enhanced that antibacterial activity of ZG film against Shewanella putrefaciens. PL combined with GA is more suitable for modifying ZG film than GA alone. Moreover, PL/GA/ZG film effectively inhibited total viable count, total volatile base nitrogen, fat oxidation and texture deterioration of tuna fillets at 4°C storage, and could extend the shelf life by 3 d.CONCLUSIONSPL/GA/ZG nanofiber film have shown promising potential application in the preservation of aquatic products as a new antibacterial and antioxidant food packaging.This article is protected by copyright. All rights reserved.

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Reaching toward underexplored targets in antibacterial drug design

Cited by 29 publications

References 48 publications

Toward a structome of Acinetobacter baumannii drug targets

Toward a structome of Acinetobacter baumannii drug targets

Bioinformatic Exploration of Metal-Binding Proteome of Zoonotic Pathogen Orientia tsutsugamushi

Preparation and characterization of zein/gelatin electrospun film loaded with ε‐polylysine and gallic acid as tuna packaging system

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