A connection between antimicrobial properties of venom peptides and microbial ATP synthase

Syed, Hiba; Tauseef, Mohammad; Ahmad, Zulfiqar

doi:10.1016/j.ijbiomac.2018.07.146

Cited by 23 publications

(11 citation statements)

References 52 publications

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“…Noteworthy is that B49Mod1 forms an amphiphilic helix with 13 hydrophobic residues on the hydrophobic face and 14 polar/charged residues on the other, a characteristic observed in membrane interacting peptides [35,36]. This observation was further shown by helical wheel projection ( Figure 1C) using HeliQuest (http://heliquest.ipmc.cnrs.fr/) [37][38][39]. Circular dichroism (CD) spectrum shows that the peptide adopts different secondary structures in different conditions, as predicted by the CD spectrum (https://capito.uni-jena.de/index.php).…”

Section: Structural Information Of B49mod1mentioning

confidence: 76%

Development and Characterization of the Shortest Anti-Adhesion Peptide Analogue of B49Mod1

2020

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Inhibition of cancer cell adhesion is an effective approach to killing adherent cancer cells. B49 and its analog B49Mod1 peptides, derived from the extracellular domain (ECD) of bone marrow stromal antigen 2 (BST-2), display anti-adhesion activity on breast cancer cells. However, the minimal sequence required for this anti-adhesion activity is unknown. Here, we further characterized the anti-adhesion activity of B49Mod1. We show that the anti-adhesion activity of B49Mod1 may require cysteine-linked disulfide bond and that the peptide is susceptible to proteolytic deactivation. Using structure-activity relationship studies, we identified an 18-Mer sequence (B18) as the minimal peptide sequence mediating the anti-adhesion activity of B49Mod1. Atomistic molecular dynamic (MD) simulations reveal that B18 forms a stable complex with the ECD of BST-2 in aqueous solution. MD simulations further reveal that B18 may cause membrane defects that facilitates peptide translocation across the bilayer. Placement of four B18 chains as a transmembrane bundle results in water channel formation, indicating that B18 may impair membrane integrity and form pores. We hereby identify B18 as the minimal peptide sequence required for the anti-adhesion activity of B49Mod1 and provide atomistic insight into the interaction of B18 with BST-2 and the cell membrane.

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Section: Structural Information Of B49mod1mentioning

confidence: 76%

Development and Characterization of the Shortest Anti-Adhesion Peptide Analogue of B49Mod1

2020

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“…25 Another phytochemical, hydroxytyrosol from olives, caused about 60% inhibition of E. coli membrane-bound F 1 F O -ATP synthase, but the repositioning of its -OH groups resulted in almost complete enzyme inhibition. 24 Some venom peptides 18 from wasp, spider, bee, and scorpion that target the F 1 F O -ATP synthase also block bacterial proliferation. These peptides bind to the βDELSEED-motif residues of F 1 .…”

Section: Drugs Targeting Fmentioning

confidence: 99%

“…24 New-generation inhibitors may be addressed to selectively kill bacterial pathogens, overcoming the increasing threat of antibiotic resistance, whereas mPTP modulators targeting the F 1 F O -ATP synthase may constitute innovative therapeutic interventions [28][29][30] to prevent cell death in diseases associated with mitochondrial dysfunctions or, conversely, to initiate the deathly pathway to lessen the proliferation of malignant cells. Although the possibility of exploiting F O subunits as drug targets has been strongly supported by bioinformatic insights, 31 the possible modulation of the drug potency, on one side by acting on drug design or structural modifications of natural compounds 18,24 and, on the other, through amino acid substitutions or posttranslational modifications on both the F 1 and F O domains, 32 still poses some technical difficulties and interrogatives.…”

Section: Introductionmentioning

confidence: 99%

A Therapeutic Role for the F1FO-ATP Synthase

et al. 2019

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Recently, the F1FO-ATP synthase, due to its dual role of life enzyme as main adenosine triphosphate (ATP) maker and of death enzyme, as ATP dissipator and putative structural component of the mitochondrial permeability transition pore (mPTP), which triggers cell death, has been increasingly considered as a drug target. Accordingly, the enzyme offers new strategies to counteract the increased antibiotic resistance. The challenge is to find or synthesize compounds able to discriminate between prokaryotic and mitochondrial F1FO-ATP synthase, exploiting subtle structural differences to kill pathogens without affecting the host. From this perspective, the eukaryotic enzyme could also be made refractory to macrolide antibiotics by chemically produced posttranslational modifications. Moreover, because the mitochondrial F1FO-ATPase activity stimulated by Ca2+ instead of by the natural modulator Mg2+ is most likely involved in mPTP formation, effectors preferentially targeting the Ca2+-activated enzyme may modulate the mPTP. If the enzyme involvement in the mPTP is confirmed, Ca2+-ATPase inhibitors may counteract conditions featured by an increased mPTP activity, such as neurodegenerative and cardiovascular diseases and physiological aging. Conversely, mPTP opening could be pharmacologically stimulated to selectively kill unwanted cells. On the basis of recent literature and promising lab findings, the action mechanism of F1 and FO inhibitors is considered. These molecules may act as enzyme modifiers and constitute new drugs to kill pathogens, improve compromised enzyme functions, and limit the deathly enzyme role in pathologies. The enzyme offers a wide spectrum of therapeutic strategies to fight at the molecular level diseases whose treatment is still insufficient or merely symptomatic.

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“…Anoplin is the shortest, amphipathic, linear α-helical antimicrobial peptide (AMP) with only 10 residues (Gly-Leu-Leu-Lys-Arg-Ile-Lys-Thr-Leu-Leu-NH 2 ) (Konno et al, 2001 ; Jittikoon, 2015 ); it also exhibits a wide range of biological activities including antibacterial (Konno et al, 2001 ; Monincová et al, 2010 ), mast cell degranulating (Cabrera et al, 2009 ), antitumor (Zhu et al, 2013 ; Da Silva et al, 2018 ; Kai et al, 2018 ), antimalarial (Carter et al, 2013 ), antifungal (Jindrichova et al, 2014 ), and anti-inflammatory activities (Zhong et al, 2020b ). Anoplin exerts its functions by direct interaction with anionic bilayers and biological membranes via ion channels (Cabrera et al, 2008 ; Leung et al, 2011 ), selectively binding to the bacterial DNA or inhibiting ATP synthase (Syed et al, 2018 ). Owing to its extremely simple structure and nonhemolytic toxicity, anoplin exhibits superiority in chemical manipulation, structure–activity relationship studies, mechanisms of action, and medical application, which has a great potential as a novel class of drugs for antibiotics and anticancer applications.…”

Section: Introductionmentioning

confidence: 99%

Advances in the Study of Structural Modification and Biological Activities of Anoplin

Huang

Jin

et al. 2020

Front. Chem.

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Anoplin is an amphipathic, α-helical bioactive peptide from wasp venom. In recent years, pharmaceutical and organic chemists discovered that anoplin and its derivatives showed multiple pharmacological activities in antibacterial, antitumor, antifungal, and antimalarial activities. Owing to the simple and unique structure and diverse biological activities, anoplin has attracted considerable research interests. This review highlights the advances in structural modification, biological activities, and the outlook of anoplin in order to provide a basis for new drug design and delivery.

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A connection between antimicrobial properties of venom peptides and microbial ATP synthase

Cited by 23 publications

References 52 publications

Development and Characterization of the Shortest Anti-Adhesion Peptide Analogue of B49Mod1

Development and Characterization of the Shortest Anti-Adhesion Peptide Analogue of B49Mod1

A Therapeutic Role for the F1FO-ATP Synthase

Advances in the Study of Structural Modification and Biological Activities of Anoplin

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