scholarly journals Functional, metal-based crosslinkers for α-helix induction in short peptides

2013 ◽  
Vol 4 (9) ◽  
pp. 3740 ◽  
Author(s):  
Sarah J. Smith ◽  
Kang Du ◽  
Robert J. Radford ◽  
F. Akif Tezcan
Keyword(s):  
Short Peptides ◽  
Α Helix

scholarly journals Controlling 310-Helix and α-Helix of Short Peptides in the Solid State

2007 ◽  
Vol 55 (5) ◽  
pp. 840-842 ◽  
Author(s):  
Yosuke Demizu ◽  
Masakazu Tanaka ◽  
Masanobu Nagano ◽  
Masaaki Kurihara ◽  
Mitsunobu Doi ◽  
...  
Keyword(s):  
Solid State ◽  
Short Peptides ◽  
Α Helix ◽  
310 Helix

scholarly journals Unfolding of α-helical 20-residue poly-glutamic acid analyzed by multiple runs of canonical molecular dynamics simulations

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4769 ◽  
Author(s):  
Naoki Ogasawara ◽  
Kota Kasahara ◽  
Ryosuke Iwai ◽  
Takuya Takahashi
Keyword(s):  
Molecular Dynamics ◽  
Glutamic Acid ◽  
Molecular Dynamics Simulations ◽  
Helical Conformation ◽  
Short Peptides ◽  
Computational Studies ◽  
Middle Region ◽  
Helix Conformation ◽  
Α Helix ◽  
Dynamics Simulations

Elucidating the molecular mechanism of helix–coil transitions of short peptides is a long-standing conundrum in physical chemistry. Although the helix–coil transitions of poly-glutamic acid (PGA) have been extensively studied, the molecular details of its unfolding process still remain unclear. We performed all-atom canonical molecular dynamics simulations for a 20-residue PGA, over a total of 19 μs, in order to investigate its helix-unfolding processes in atomic resolution. Among the 28 simulations, starting with the α-helical conformation, all showed an unfolding process triggered by the unwinding of terminal residues, rather than by kinking and unwinding of the middle region of the chain. The helix–coil–helix conformation which is speculated by the previous experiments was not observed. Upon comparison between the N- and C-termini, the latter tended to be unstable and easily unfolded. While the probabilities of helix elongation were almost the same among the N-terminal, middle, and C-terminal regions of the chain, unwinding of the helix was enriched at the C-terminal region. The turn and 310-helix conformations were kinetic intermediates in the formation and deformation of α-helix, consistent with the previous computational studies for Ala-based peptides.

Design and synthesis of small molecule initiators of α-helix structure in short peptides in water

Peptides 1994 ◽  
1995 ◽  
pp. 692-693 ◽  
Author(s):  
J. P. Meara ◽  
B. Cao ◽  
J. Urban ◽  
H. Nakanishi ◽  
E. Yeung ◽  
...  
Keyword(s):  
Small Molecule ◽  
Short Peptides ◽  
Design And Synthesis ◽  
Helix Structure ◽  
Α Helix

Effect of Temperature and pH on the Secondary Structure and Denaturation Process of Jumbo Squid Hepatopancreas Cathepsin D.

2019 ◽  
Vol 26 (7) ◽  
pp. 532-541 ◽  
Author(s):  
Cadena-Cadena Francisco ◽  
Cárdenas-López José Luis ◽  
Ezquerra-Brauer Josafat Marina ◽  
Cinco-Moroyoqui Francisco Javier ◽  
López-Zavala Alonso Alexis ◽  
...  
Keyword(s):  
Circular Dichroism ◽  
Secondary Structure ◽  
Cathepsin D ◽  
Thermal Denaturation ◽  
Protein Denaturation ◽  
Marine Organisms ◽  
Effect Of Temperature ◽  
Jumbo Squid ◽  
Α Helix ◽  
Circular Dichroïsm

Background: Cathepsin D is a lysosomal enzyme that is found in all organisms acting in protein turnover, in humans it is present in some types of carcinomas, and it has a high activity in Parkinson's disease and a low activity in Alzheimer disease. In marine organisms, most of the research has been limited to corroborate the presence of this enzyme. It is known that cathepsin D of some marine organisms has a low thermostability and that it has the ability to have activity at very acidic pH. Cathepsin D of the Jumbo squid (Dosidicus gigas) hepatopancreas was purified and partially characterized. The secondary structure of these enzymes is highly conserved so the role of temperature and pH in the secondary structure and in protein denaturation is of great importance in the study of enzymes. The secondary structure of cathepsin D from jumbo squid hepatopancreas was determined by means of circular dichroism spectroscopy. Objective: In this article, our purpose was to determine the secondary structure of the enzyme and how it is affected by subjecting it to different temperature and pH conditions. Methods: Circular dichroism technique was used to measure the modifications of the secondary structure of cathepsin D when subjected to different treatments. The methodology consisted in dissecting the hepatopancreas of squid and freeze drying it. Then a crude extract was prepared by mixing 1: 1 hepatopancreas with assay buffer, the purification was in two steps; the first step consisted of using an ultrafiltration membrane with a molecular cut of 50 kDa, and the second step, a pepstatin agarose resin was used to purification the enzyme. Once the enzyme was purified, the purity was corroborated with SDS PAGE electrophoresis, isoelectric point and zymogram. Circular dichroism is carried out by placing the sample with a concentration of 0.125 mg / mL in a 3 mL quartz cell. The results were obtained in mdeg (millidegrees) and transformed to mean ellipticity per residue, using 111 g/mol molecular weight/residue as average. Secondary-structure estimation from the far-UV CD spectra was calculated using K2D Dichroweb software. Results: It was found that α helix decreases at temperatures above 50 °C and above pH 4. Heating the enzyme above 70°C maintains a low percentage of α helix and increases β sheet. Far-UV CD measurements of cathepsin D showed irreversible thermal denaturation. The process was strongly dependent on the heating rate, accompanied by a process of oligomerization of the protein that appears when the sample is heated, and maintained a certain time at this temperature. An amount typically between 3 and 4% α helix of their secondary structure remains unchanged. It is consistent with an unfolding process kinetically controlled due to the presence of an irreversible reaction. The secondary structure depends on pH, and a pH above 4 causes α helix structures to be modified. Conclusion: In conclusion, cathepsin D from jumbo squid hepatopancreas showed retaining up to 4% α helix at 80°C. The thermal denaturation of cathepsin D at pH 3.5 is under kinetic control and follows an irreversible model.

The Inhibition of Polysialyltranseferase ST8SiaIV Through Heparin Binding to Polysialyltransferase Domain (PSTD)

2019 ◽  
Vol 15 (5) ◽  
pp. 486-495 ◽  
Author(s):  
Li-Xin Peng ◽  
Xue-Hui Liu ◽  
Bo Lu ◽  
Si-Ming Liao ◽  
Feng Zhou ◽  
...  
Keyword(s):  
Fluorescence Quenching ◽  
Polysialic Acid ◽  
Neuronal Cell ◽  
Cd Spectroscopy ◽  
Migration And Invasion ◽  
Heparin Binding ◽  
Clinical Prognosis ◽  
Quenching Analysis ◽  
Different Types ◽  
Α Helix

Background:The polysialic acid (polySia) is a unique carbohydrate polymer produced on the surface Of Neuronal Cell Adhesion Molecule (NCAM) in a number of cancer cells, and strongly correlates with the migration and invasion of tumor cells and with aggressive, metastatic disease and poor clinical prognosis in the clinic. Its synthesis is catalyzed by two polysialyltransferases (polySTs), ST8SiaIV (PST) and ST8SiaII (STX). Selective inhibition of polySTs, therefore, presents a therapeutic opportunity to inhibit tumor invasion and metastasis due to NCAM polysialylation. Heparin has been found to be effective in inhibiting the ST8Sia IV activity, but no clear molecular rationale. It has been found that polysialyltransferase domain (PSTD) in polyST plays a significant role in influencing polyST activity, and thus it is critical for NCAM polysialylation based on the previous studies.Objective:To determine whether the three different types of heparin (unfractionated hepain (UFH), low molecular heparin (LMWH) and heparin tetrasaccharide (DP4)) is bound to the PSTD; and if so, what are the critical residues of the PSTD for these binding complexes?Methods:Fluorescence quenching analysis, the Circular Dichroism (CD) spectroscopy, and NMR spectroscopy were used to determine and analyze interactions of PSTD-UFH, PSTD-LMWH, and PSTD-DP4.Results:The fluorescence quenching analysis indicates that the PSTD-UFH binding is the strongest and the PSTD-DP4 binding is the weakest among these three types of the binding; the CD spectra showed that mainly the PSTD-heparin interactions caused a reduction in signal intensity but not marked decrease in α-helix content; the NMR data of the PSTD-DP4 and the PSTDLMWH interactions showed that the different types of heparin shared 12 common binding sites at N247, V251, R252, T253, S257, R265, Y267, W268, L269, V273, I275, and K276, which were mainly distributed in the long α-helix of the PSTD and the short 3-residue loop of the C-terminal PSTD. In addition, three residues K246, K250 and A254 were bound to the LMWH, but not to DP4. This suggests that the PSTD-LMWH binding is stronger than the PSTD-DP4 binding, and the LMWH is a more effective inhibitor than DP4.Conclusion:The findings in the present study demonstrate that PSTD domain is a potential target of heparin and may provide new insights into the molecular rationale of heparin-inhibiting NCAM polysialylation.

Scorpion toxin-potassium channel interaction law and its applications.

2020 ◽  
Vol 01 ◽  
Author(s):  
Zheng Zuo ◽  
Zongyun Chen ◽  
Zhijian Cao ◽  
Wenxin Li ◽  
Yingliang Wu
Keyword(s):  
Potassium Channel ◽  
Scorpion Toxin ◽  
Scorpion Toxins ◽  
Toxin Binding ◽  
Channel Interaction ◽  
Binding Interface ◽  
Α Helix ◽  
Interaction Law ◽  
Binding Interfaces ◽  
Β Sheet

: The scorpion toxins are the largest potassium channel-blocking peptide family. The understanding of toxin binding interfaces is usually restricted by two classical binding interfaces: one is the toxin α-helix motif, the other is the antiparallel β-sheet motif. In this review, such traditional knowledge was updated by another two different binding interfaces: one is BmKTX toxin using the turn motif between the α-helix and antiparallel β-sheet domains as the binding interface, the other is Ts toxin using turn motif between the β-sheet in the N-terminal and α-helix domains as the binding interface. Their interaction analysis indicated that the scarce negatively charged residues in the scorpion toxins played a critical role in orientating the toxin binding interface. In view of the toxin negatively charged amino acids as “binding interface regulator”, the law of scorpion toxin-potassium channel interaction was proposed, that is, the polymorphism of negatively charged residue distribution determines the diversity of toxin binding interfaces. Such law was used to develop scorpion toxin-potassium channel recognition control technique. According to this technique, three Kv1.3 channel-targeted peptides, using BmKTX as the template, were designed with the distinct binding interfaces from that of BmKTX through modulating the distribution of toxin negatively charged residues. In view of the potassium channel as the common targets of different animal toxins, the proposed law was also shown to helpfully orientate the binding interfaces of other animal toxins. Clearly, the toxin-potassium channel interaction law would strongly accelerate the research and development of different potassium channelblocking animal toxins in the future.

Aromatic identity, electronic substitution, and sequence in amphiphilic tripeptide self-assembly

Soft Matter ◽  
2018 ◽  
Vol 14 (45) ◽  
pp. 9168-9174 ◽  
Author(s):  
Jugal Kishore Sahoo ◽  
Calvin Nazareth ◽  
Michael A. VandenBerg ◽  
Matthew J. Webber
Keyword(s):  
Self Assembly ◽  
Short Peptides ◽  
Design Rules ◽  
Sequence Variations

The design rules for self-assembly of short peptides are assessed using a combination of chemical and sequence variations.

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