Three-dimensional structure of Phyllomedusin, a NK1 receptor agonist bound to dodecylphosphocholine micelles

Ganjiwale, Anjali; Cowsik, Sudha M.

doi:10.1016/j.jsb.2009.04.008

Cited by 6 publications

(16 citation statements)

References 64 publications

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“…A previous report also showed evidences of formation of pores and cracks by Ctr on the surfaces of bacterial cell wall . To gain further insights on the structural basis of Ctr for its high antibacterial potency and its mode of action, the structure of Ctr was determined in anionic SDS micelles and zwitterionic DPC micelles, which approximate bacterial and eukaryotic membranes, respectively . The solution structures of Ctr bound to micelles presented here clearly show a flexible N‐terminal region with hydrophobic residues of the peptide and a well‐defined amphipathic α‐helix at C‐terminal with positively charged residues (Lys18 and Lys19) remained flexible.…”

Section: Discussionmentioning

confidence: 64%

“…7 To gain further insights on the structural basis of Ctr for its high antibacterial potency and its mode of action, the structure of Ctr was determined in anionic SDS micelles and zwitterionic DPC micelles, which approximate bacterial and eukaryotic membranes, respectively. [48][49][50][51][52][53][54] The solution structures of Ctr bound to micelles presented here clearly show a flexible N-terminal region with hydrophobic residues of the peptide and a welldefined amphipathic a-helix at C-terminal with positively charged residues (Lys18 and Lys19) remained flexible. Hydrophobic amino acids with aromatic side chains, such as phenylalanine and tryptophan residues, are known to serve as a membrane anchor in transmembrane helices.…”

Section: Discussionmentioning

confidence: 99%

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Solution structures and model membrane interactions of Ctriporin, an anti‐methicillin‐resistant Staphylococcus aureus Peptide from Scorpion Venom

et al. 2014

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Ctriporin peptide (Ctr), a novel antimicrobial peptide isolated from the venom of the scorpion Chaerilus tricostatus, shows a broad-spectrum of antimicrobial activity and is able to inhibit antibiotic resistant pathogens, including Methicillin resistant Staphylococcus aureus, Methicillin Resistant Coagulase-negative Staphylococcus, and Penicillin Resistant Staphylococcus epidermidis strains. To understand the active conformation of the Ctr peptide in membranes, we have investigated the interaction of Ctr with the negatively charged and zwitterionic membrane-mimetic micelles such as sodium dodecyl sulphate (SDS) and n-dodecylphosphocholine (DPC), respectively. The interactions were studied using fluorescence and circular dichroism (CD) spectroscopy. Fluorescence experiments revealed that the N-terminus tryptophan residue of Ctr interacted with the hydrophobic core of the membrane mimicking micelles. The CD results suggest that interactions with membrane-mimetic micelles induce an α-helix conformation in Ctr. Moreover, we have determined the solution structures of Ctr in SDS and DPC micelles using nuclear magnetic resonance (NMR) spectroscopy. The structural comparison of Ctr in the presence of SDS and DPC micelles showed significant conformational changes. The observed structural differences of Ctr in anionic versus zwitterionic membrane-mimetic micelles suggest that the mode of interaction of this peptide may be different in two environments which may account for its ability to differentiate bacterial and eukaryotic cell membrane.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Solution structures and model membrane interactions of Ctriporin, an anti‐methicillin‐resistant Staphylococcus aureus Peptide from Scorpion Venom

et al. 2014

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“…The C‐terminus of SP and hHK‐1 are similar so we propose that hHK‐1 would activate but produce less desensitization due to increase in helix length. As reported for other NK1 agonists, namely Physalaemin, Kassinin, Eledoisin where increase in helix length alters activity but not the selectivity of the receptor . However, the results are very preliminary and more study needs to be done.…”

Section: Discussionmentioning

confidence: 80%

“…As reported for other NK1 agonists, namely Physalaemin, Kassinin, Eledoisin where increase in helix length alters activity but not the selectivity of the receptor. 37,41,44 However, the results are very preliminary and more study needs to be done.…”

Section: Discussionmentioning

confidence: 99%

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Membrane‐induced structure of novel human tachykinin hemokinin‐1 (hHK1)

Ganjiwale

Cowsik

2015

Biopolymers

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PPT-C encoded hemokinin-1(hHK-1) of Homo sapiens (TGKASQFFGLM) is a structurally distinct neuropeptide among the tachykinin family that participate in the NK-1 receptor downstream signaling processes. Subsequently, signal transduction leads to execution of various effector functions which includes aging, immunological, and central nervous system (CNS) regulatory actions. However the conformational pattern of ligand receptor binding is unclear. The three-dimensional structure of the hemokinin-1 in aqueous and micellar environment has been studied by one and two-dimensional proton nuclear magnetic resonance (2D 1H-NMR spectroscopy) and distance geometry calculations. Data shows that hemokinin-1 was unstructured in aqueous environment; anionic detergent SDS induces α-helix formation. Proton NMR assignments have been carried out with the aid of correlation spectroscopy (gradient-COSY and TOCSY) and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The inter proton distances and dihedral angle constraints obtained from the NMR data have been used in torsion angle dynamics algorithm for NMR applications (CYANA) to generate a family of structures, which have been refined using restrained energy minimization and dynamics. Helical conformation is observed from residue K3-M11. The conformational range of the peptide revealed by NMR studies has been analyzed in terms of characteristic secondary features. Observed conformational features have been compared to that of Substance P potent NK1 agonist. Thus the report provides a structural insight to study hHK-1-NK1 interaction that is essential for hHK1 based signaling events.

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Development of Neuropeptide Hemokinin-1 Analogues with Antimicrobial and Wound-Healing Activity

Yao

Zhang

et al. 2023

J. Med. Chem.

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Wound healing is a complex process that can be delayed in some pathological conditions, such as infection and diabetes. Following skin injury, the neuropeptide substance P (SP) is released from peripheral neurons to promote wound healing by multiple mechanisms. Human hemokinin-1 (hHK-1) has been identified as an SP-like tachykinin peptide. Surprisingly, hHK-1 shares similar structural features with antimicrobial peptides (AMPs), but it does not display efficient antimicrobial activity. Therefore, a series of hHK-1 analogues were designed and synthesized. Among these analogues, AH-4 was found to display the greatest antimicrobial activity against a broad spectrum of bacteria. Furthermore, AH-4 rapidly killed bacteria by membrane disruption, similar to most AMPs. More importantly, AH-4 showed favorable healing activity in all tested mouse full-thickness excisional wound models. Overall, this study suggests that the neuropeptide hHK-1 can be used as a desirable template for developing promising therapeutics with multiple functions for wound healing.

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Three-dimensional structure of Phyllomedusin, a NK1 receptor agonist bound to dodecylphosphocholine micelles

Cited by 6 publications

References 64 publications

Solution structures and model membrane interactions of Ctriporin, an anti‐methicillin‐resistant Staphylococcus aureus Peptide from Scorpion Venom

Solution structures and model membrane interactions of Ctriporin, an anti‐methicillin‐resistant Staphylococcus aureus Peptide from Scorpion Venom

Membrane‐induced structure of novel human tachykinin hemokinin‐1 (hHK1)

Development of Neuropeptide Hemokinin-1 Analogues with Antimicrobial and Wound-Healing Activity

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