scholarly journals Mixed Chirality α-Helix in a Stapled Bicyclic and a Linear Antimicrobial Peptide Revealed by X-Ray Crystallography

2021 ◽  
Author(s):  
stéphane Baeriswyl ◽  
Hippolyte Personne ◽  
Ivan Di Bonaventura ◽  
Thilo Köhler ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Md Simulations ◽  
Isobutyric Acid ◽  
Cd Spectra ◽  
X Ray ◽  
X Ray Crystallography ◽  
Left Handed ◽  
Amino Isobutyric Acid ◽  
Α Helix ◽  
Protein Environment

<p></p><p>The peptide α-helix is right-handed when containing amino acids with L-chirality, and left-handed with D-chirality, however mixed chirality peptides generally do not form α-helices unless the non-natural residue amino-isobutyric acid is used as helix inducer. Herein we report the first X-ray crystal structures of mixed chirality α-helices in short peptides comprising only natural residues at the example of a stapled bicyclic and a linear membrane disruptive amphiphilic antimicrobial peptide (AMP) containing seven L- and four D-residues, as complexes of fucosylated analogs with the bacterial lectin LecB. The mixed chirality α-helices are superimposable to their parent homochiral α-helices and form under similar conditions as shown by CD spectra and MD simulations but are resistant to proteolysis. The observation of mixed chirality α-helix with only natural residues in the protein environment of LecB suggests a vast unexplored territory of α-helical mixed chirality sequences and their possible use for optimizing bioactive α-helical peptides.</p><br><p></p>

scholarly journals Mixed Chirality α-Helix in a Stapled Bicyclic and a Linear Antimicrobial Peptide Revealed by X-Ray Crystallography

2021 ◽  
Author(s):  
stéphane Baeriswyl ◽  
Hippolyte Personne ◽  
Ivan Di Bonaventura ◽  
Thilo Köhler ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Bioactive Peptides ◽  
Multidrug Resistant ◽  
Isobutyric Acid ◽  
Resistant Bacteria ◽  
X Ray ◽  
X Ray Crystallography ◽  
Left Handed ◽  
Amino Isobutyric Acid ◽  
Α Helix ◽  
Dynamics Simulations

<p>The peptide α-helix is right-handed when containing amino acids with L-chirality, and left-handed with D-chirality. What happens in between is largely unknown, however α-helices have not been reported with mixed chirality sequences unless a strong non-natural helix inducer such as amino-isobutyric acid was used. Herein we report the discovery of a membrane disruptive amphiphilic antimicrobial undecapeptide containing seven L- and four D-residues forming a stable right-handed α-helix in stapled bicyclic and linear forms. The α-helical fold is evidenced by X-ray crystallography and supported in solution by circular dichroism spectra as well as molecular dynamics simulations. The linear mixed chirality peptide is as active as the L-sequence against multidrug resistant bacteria but shows no hemolysis and full stability against serum proteolysis. Searching for mixed chirality analogs preserving folding might be generally useful to optimize α-helical bioactive peptides. </p>

scholarly journals Mixed Chirality α-Helix in a Stapled Bicyclic and a Linear Antimicrobial Peptide Revealed by X-Ray Crystallography

2021 ◽  
Author(s):  
stéphane Baeriswyl ◽  
Hippolyte Personne ◽  
Ivan Di Bonaventura ◽  
Thilo Köhler ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Bioactive Peptides ◽  
Multidrug Resistant ◽  
Isobutyric Acid ◽  
Resistant Bacteria ◽  
X Ray ◽  
X Ray Crystallography ◽  
Left Handed ◽  
Amino Isobutyric Acid ◽  
Α Helix ◽  
Dynamics Simulations

<p>The peptide α-helix is right-handed when containing amino acids with L-chirality, and left-handed with D-chirality. What happens in between is largely unknown, however α-helices have not been reported with mixed chirality sequences unless a strong non-natural helix inducer such as amino-isobutyric acid was used. Herein we report the discovery of a membrane disruptive amphiphilic antimicrobial undecapeptide containing seven L- and four D-residues forming a stable right-handed α-helix in stapled bicyclic and linear forms. The α-helical fold is evidenced by X-ray crystallography and supported in solution by circular dichroism spectra as well as molecular dynamics simulations. The linear mixed chirality peptide is as active as the L-sequence against multidrug resistant bacteria but shows no hemolysis and full stability against serum proteolysis. Searching for mixed chirality analogs preserving folding might be generally useful to optimize α-helical bioactive peptides. </p>

scholarly journals Mixed Chirality α-Helix in a Stapled Bicyclic and a Linear Antimicrobial Peptide Revealed by X-Ray Crystallography

2021 ◽  
Author(s):  
stéphane Baeriswyl ◽  
Hippolyte Personne ◽  
Ivan Di Bonaventura ◽  
Thilo Köhler ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Bioactive Peptides ◽  
Multidrug Resistant ◽  
Isobutyric Acid ◽  
Resistant Bacteria ◽  
X Ray ◽  
X Ray Crystallography ◽  
Left Handed ◽  
Amino Isobutyric Acid ◽  
Α Helix ◽  
Dynamics Simulations

<p>The peptide α-helix is right-handed when containing amino acids with L-chirality, and left-handed with D-chirality. What happens in between is largely unknown, however α-helices have not been reported with mixed chirality sequences unless a strong non-natural helix inducer such as amino-isobutyric acid was used. Herein we report the discovery of a membrane disruptive amphiphilic antimicrobial undecapeptide containing seven L- and four D-residues forming a stable right-handed α-helix in stapled bicyclic and linear forms. The α-helical fold is evidenced by X-ray crystallography and supported in solution by circular dichroism spectra as well as molecular dynamics simulations. The linear mixed chirality peptide is as active as the L-sequence against multidrug resistant bacteria but shows no hemolysis and full stability against serum proteolysis. Searching for mixed chirality analogs preserving folding might be generally useful to optimize α-helical bioactive peptides. </p>

scholarly journals A mixed chirality α-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography

2021 ◽  
Author(s):  
Stéphane Baeriswyl ◽  
Hippolyte Personne ◽  
Ivan Di Bonaventura ◽  
Thilo Köhler ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Crystal Structures ◽  
X Ray ◽  
X Ray Crystallography ◽  
Α Helix

We report the first X-ray crystal structures of mixed chirality α-helices comprising only natural residues as the example of bicyclic and linear membrane disruptive amphiphilic antimicrobial peptides containing seven l- and four d-residues.

One-pot synthesis of 5-(8-ethoxycarbonyl-1-naphthyl)-10,15,20-triphenyl porphyrin (ENTPP) and spontaneous resolution upon crystallization

2011 ◽  
Vol 15 (03) ◽  
pp. 197-201 ◽  
Author(s):  
Juanxia Yang ◽  
Jiaxun Jiang ◽  
Weiguang Fang ◽  
Xiaoxu Kai ◽  
Chuanjiang Hu ◽  
...  
Keyword(s):  
Soret Band ◽  
Ester Group ◽  
Spontaneous Resolution ◽  
Cd Spectra ◽  
One Pot ◽  
Nmr Spectrum ◽  
X Ray ◽  
X Ray Crystallography ◽  
H Nmr ◽  
Entire Structure

5-(8-ethoxycarbonyl-1-naphthyl)-10,15,20-triphenyl porphyrin (ENTPP) has been synthesized in a one-pot reaction, and the corresponding chiral crystalline samples have been obtained by spontaneous resolution. 1 H NMR spectrum suggests it is mononaphthyl substituted species and an ethyl group is over the porphyrin plane. The structure has been further confirmed by X-ray crystallography. ENTPP·C6H14 (C57H50N4O2 ): monoclinic, P21, a = 10.707(2) Å, b = 12.203(2) Å, c = 17.858(4) Å, β = 103.06(3)°, V = 2272.8(8) Å3, Z = 2. The 8-position substituent, ester group, lies above the porphyrin plane and leads to the conformational chirality. The entire structure is built up with homochiral molecules, which leads to a chiral crystal through packing in P21 space group. Circular dichroism (CD) spectra have exhibited remarkable absorptions in the Soret band region, which further confirms the homochirality of the crystalline samples.

Correlation Between Water Molecules Identified in Atomic Models of Beta-Galactosidase Determined by Cryo-EM and X-Ray Crystallography

2020 ◽  
Author(s):  
Florentina Tofoleanu ◽  
Lesley Earl ◽  
Frank Pickard ◽  
Bernard Brooks
Keyword(s):  
Crystal Structures ◽  
Binding Sites ◽  
Md Simulations ◽  
Water Molecules ◽  
Water Residence Time ◽  
Solvent Exposure ◽  
X Ray ◽  
Protein Residues ◽  
X Ray Crystallography ◽  
Beta Galactosidase

<p>We start from the water placement in cryo-EM maps and in X-ray crystal structures of beta-galactosidase. We apply MD simulations to analyze the behavior of the placed water, and how they are bound to the protein residues. We analyze the solvent exposure of binding sites for water, and the water residence time at these locations. Through a statistical analysis, we conclude that water placed by cryo-EM has a similar behavior to conserved water across multiple crystal structures.</p>

The dynamic role of distal side residues in heme hydroperoxidase catalysis. Interplay between X-ray crystallography and ab initio MD simulations

2010 ◽  
Vol 500 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Pietro Vidossich ◽  
Mercedes Alfonso-Prieto ◽  
Xavi Carpena ◽  
Ignacio Fita ◽  
Peter C. Loewen ◽  
...  
Keyword(s):  
Ab Initio ◽  
Md Simulations ◽  
X Ray ◽  
X Ray Crystallography ◽  
Distal Side ◽  
Ab Initio Md

N-Glycoside Complexes of Nickel(II); Probing Carbohydrate - Transition Metal Interactions

2009 ◽  
Vol 62 (3) ◽  
pp. 265 ◽  
Author(s):  
Dale Jones ◽  
Marcelis van Holst ◽  
Shigenobu Yano ◽  
Tomoaki Tanase ◽  
Janice Aldrich-Wright
Keyword(s):  
Chelate Ring ◽  
Chair Conformation ◽  
Nickel Atom ◽  
Cd Spectra ◽  
Metal Centre ◽  
Ring Conformation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Metal Interactions ◽  
Helical Configuration

Nickel(ii) complexes prepared from d- and l-arabinose (d-ara and l-ara) and 1,2-diaminoethane (en), [Ni(en-d-ara)2](ClO4)2·2H2O 1 and [Ni(en-l-ara)2](ClO4)2·2H2O 2 (where en-d-ara is 1-((2-aminoethyl)amino)-1-deoxy-d-arabinose) were synthesized and characterized by absorption spectroscopy, circular dichroism (CD), and X-ray crystallography. The CD spectra of 1 and 2 in the d–d transition region indicate a C2 chiral configuration around the metal centre. X-ray crystallography of 1 revealed that two 1-((2-aminoethyl)amino)-1-deoxy-d-arabinose ligands coordinate to the nickel atom in nearly C2 symmetry, through the C(2) hydroxy group of the arabinose moiety and two nitrogen atoms of the diamine in a meridional mode. This results in a Λ-C2-helical configuration around the metal centre. The arabinose ring adopts the rare α-1C4 chair conformation and the carbohydrate–chelate ring conformation is δ.

scholarly journals Informing NMR experiments with molecular dynamics simulations to characterize the dominant activated state of the KcsA ion channel

2020 ◽  
Author(s):  
Sergio Perez-Conesa ◽  
Eric G. Keeler ◽  
Dongyu Zhang ◽  
Lucie Delemotte ◽  
Ann E McDermott
Keyword(s):  
Molecular Dynamics ◽  
Chemical Shifts ◽  
Md Simulations ◽  
X Ray ◽  
Nmr Chemical Shifts ◽  
X Ray Crystallography ◽  
Activated State ◽  
State Present ◽  
Dynamics Simulations ◽  
Inference Techniques

As the first potassium channel with a X-ray structure determined, and given its homol- ogy to eukaryotic channels, the pH-gated prokaryotic channel KcsA has been extensively studied. Nevertheless, questions related in particular to the allosteric coupling between its gates remain open. The many currently available X-ray crystallography structures appear to correspond to various stages of activation and inactivation, offering insights into the molecular basis of these mechanisms. Since these studies have required mutations, com- plexation with antibodies, and substitution of detergents for lipids, examining the channel under more native conditions is desirable. Solid-state NMR (SSNMR) can be used to study the wild-type protein under activating conditions (low pH), at room temperature, and in bacteriomimetic liposomes. In this work, we sought to structurally assign the acti- vated state present in SSNMR experiments. We used a combination of molecular dynamics (MD) simulations, chemical shift prediction algorithms, and Bayesian inference techniques to determine which of the most plausible X-ray structures resolved to date best represents the activated state captured in SSNMR. We first identified specific nuclei with simulated NMR chemical shifts that differed significantly when comparing partially open vs. fully open ensembles from MD simulations. The simulated NMR chemical shifts for those spe- cific nuclei were then compared to experimental ones, revealing that the simulation of the partially open state was in good agreement with the SSNMR data. Nuclei that discrimi- nate effectively between partially and fully open states belong to residues spread over the sequence and provide a molecular level description of the conformational change.

The stability and screw sense of the α -helix in poly- β -benzyl-L-aspartate

1960 ◽  
Vol 259 (1296) ◽  
pp. 110-128 ◽  
Keyword(s):  
Optical Rotatory Dispersion ◽  
Molecular Models ◽  
X Ray Diffraction ◽  
X Ray ◽  
Left Handed ◽  
The Difference ◽  
Diffraction Patterns ◽  
The Stability ◽  
Α Helix ◽  
The Right

A number of polymers and copolymers containing β -benzyl-L-aspartate has been prepared and their optical rotatory dispersion in a variety of solvents has been measured. The results of these measurements together with studies of infra-red spectra, X-ray diffraction patterns, deuteration rates and molecular models lead to the following conclusions. (i) The α -helical form of poly- β -benzyl-L-aspartate is considerably less stable relative to the solvated randomly coiled form than that of poly- γ -benzyl-L-glutamate. (ii) The left-handed α -helix of poly- β -benzyl-L-aspartate is more stable than the right-handed one. (iii) The difference in stability between the two senses of α -helix is much less in the case of poly- β -benzyl-L-aspartate than in that of poly- γ -benzyl-L-glutamate or poly-L-alanine.

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