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

Abstract

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.

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

“…The neuropeptide hHK-1 shares similar structural features with AMPs, such as the helical structure, positive charge, hydrophobicity, and amphiphilicity (Figure A) . Although hHK-1 has been reported to display direct antimicrobial activity, its potency is far from satisfactory.…”

“…The neuropeptide hHK-1 shares similar structural features with AMPs, such as the helical structure, positive charge, hydrophobicity, and amphiphilicity (Figure 1A). 39 Although hHK-1 has been reported to display direct antimicrobial activity, its potency is far from satisfactory. To obtain ideal therapeutic agents that combine antimicrobial and pro-regenerative activity for wound healing, a modification strategy for AMPs was used for designing analogues of hHK-1.…”

Nuclear Magnetic Resonance Investigation of the Effect of pH on Micelle Formation by the Amino Acid‐Based Surfactant Undecyl l‐Phenylalaninate

“…An analysis of intramolecular und‐Phe cross peaks was performed as well to investigate the orientation of the und‐Phe aromatic ring relative to the micelle core. Quantitative ROESY analyses can also be used to measure interatomic distances by monitoring ROESY cross peak intensity as a function of mixing time (Ammalahti, Bardet, Molko, & Cadet, ; Ganjiwale & Cowsik, ; Hilton, Chmurny, & Muschik, ; Thiele, Petzold, & Schleucher, ). Finally, combining NMR diffusion and two‐dimensional NMR experiments has been shown to provide complementary information about the size and structure of micellar aggregates (Cho et al, ; Denkova, Van Lokeren, Verbruggen, & Willem, , ; Morris, Becker, Valle, Warner, & Larive, ).…”

A design of experiments concept for the minimization of nonspecific peptide adsorption in the mass spectrometric determination of substance P and related hemokinin‐1

“…This lack of knowledge may be based on the high variability of SP blood levels caused by distinct analytical techniques and sample preparation methods [6][7][8]. The determination of SP and HK-1 blood levels are predominantly executed by immunoassays, which often lack the required selectivity to differentiate between SP and HK-1 due to crossreactivity [9,10]. Therefore, the measurement of SP and HK-1 by LC-MS/MS is a promising, highly selective alternative.…”