Exploration of α/β/γ-peptidomimetics design for BH3 helical domain.

2022 ◽  
Author(s):  
Young-Hee Shin ◽  
Hyunjun Yang
Keyword(s):  
Amino Acid ◽  
Secondary Structures ◽  
Amino Acid Residues ◽  
Helical Domain ◽  
Helix Mimetics ◽  
Α Helix

Systematic incorportation of ring-constrained β- and γ-amino acid residues to α-helix mimetics engenders stable helical secondary structures. In this paper, functional α/β/γ-helical peptidomimetics were explored for the mimicry of BH3...

Modèle topologique de la structure d’un antiport vacuolaire de type NHX chez la vigne cultivée (Vitis vinifera)

Botany ◽  
2009 ◽  
Vol 87 (3) ◽  
pp. 339-347 ◽  
Author(s):  
Mohsen Hanana ◽  
Olivier Cagnac ◽  
Ahmed Mliki ◽  
Eduardo Blumwald
Keyword(s):  
Amino Acid ◽  
Vitis Vinifera ◽  
Molecular Mass ◽  
Electrostatic Interactions ◽  
Functional Characterization ◽  
Terminal Region ◽  
Vitis Vinifera L ◽  
Amino Acid Residues ◽  
Transmembrane Segments ◽  
Α Helix

After identifying and isolating a grapevine ( Vitis vinifera L.) NHX vacuolar antiporter and before initializing functional genomic studies, we juged necessary to acquire a minimum of knowledge about the VvNHX1 protein. Thus, we realized a bioinformatic analysis to determine its basic characteristics and to get structural informations that could guide us through the functional characterization. We have determined important physico-chemical parameters (molecular mass, isoelectric point, hydrophobic regions, etc.) and obtained interesting structural data (primary, secondary, and tertiary structures; conserved domains and interaction motives; etc.). The VvNHX1 gene, which encodes this 541 amino-acid protein with a predicted molecular mass of 60 kDa, is made of 14 exons and measures 6.5 kb. The amino-acidic composition of this protein is very important, in particular, for the establishment of the α-helix structure, which represents more than 50% of the protein, but also for charge distribution, which generates critical electrostatic interactions for the ionic flux. The secondary structure of VvNHX1 contains multiple transmembrane α-helix segments that are made of hydrophobic amino-acid residues, thus facilitating its insertion in the membrane. Globally, VvNHX1 has one hydrophobic N-terminal region, made of 10 transmembrane segments with 440 amino-acid residues, and one hydrophilic C-terminal region, made of 100 residues. The region located between the fourth and fifth transmembrane segments represents, with its structure mainly helicoidal and the presence of a favourable electrostatic environment, the pore where cation flux is performed across the membrane. VvNHX1 contains various interaction domains as well as several putative posttranslational modification sites, mainly at the C-terminus but also at the N-terminus, that play an important part in regulating protein activities, influence protein structural stability, or interact with other proteins or signalling molecules.

scholarly journals Theoretical study of two-photon circular dichroism on molecular structures simulating aromatic amino acid residues in proteins with secondary structures

RSC Advances ◽  
2014 ◽  
Vol 4 (105) ◽  
pp. 60974-60986 ◽  
Author(s):  
Yuly Vesga ◽  
Carlos Diaz ◽  
Florencio E. Hernandez
Keyword(s):  
Circular Dichroism ◽  
Comparative Analysis ◽  
Theoretical Study ◽  
Secondary Structures ◽  
Molecular Structures ◽  
Random Coil ◽  
Amino Acid Residues ◽  
Two Photon ◽  
Α Helix ◽  
Circular Dichroïsm

Calculation and comparative analysis of the theoretical two-photon circular dichroism (TPCD) spectra of l-His, l-Phe, and l-Tyr simulating residues in proteins with secondary structures (α-helix, β-strand and random coil), down to the far-UV region (FUV).

scholarly journals Noncharged amino acid residues at the solvent-exposed positions in the middle and at the C terminus of the α-helix have the same helical propensity

2003 ◽  
Vol 12 (6) ◽  
pp. 1169-1176 ◽  
Author(s):  
Dmitri N. Ermolenko ◽  
John M. Richardson ◽  
George I. Makhatadze
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
C Terminus ◽  
Α Helix

scholarly journals The Respiratory Syncytial Virus M2-1 Protein Forms Tetramers and Interacts with RNA and P in a Competitive Manner

2009 ◽  
Vol 83 (13) ◽  
pp. 6363-6374 ◽  
Author(s):  
Thi-Lan Tran ◽  
Nathalie Castagné ◽  
Virginie Dubosclard ◽  
Sylvie Noinville ◽  
Emmanuelle Koch ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Amino Acid ◽  
Rna Binding ◽  
Amino Acid Residues ◽  
Polymerase Complex ◽  
Bacterial Rna ◽  
Infected Cells ◽  
Syncytial Virus ◽  
Α Helix ◽  
Zinc Binding Domain

ABSTRACT The respiratory syncytial virus (RSV) M2-1 protein is an essential cofactor of the viral RNA polymerase complex and functions as a transcriptional processivity and antitermination factor. M2-1, which exists in a phosphorylated or unphosphorylated form in infected cells, is an RNA-binding protein that also interacts with some of the other components of the viral polymerase complex. It contains a CCCH motif, a putative zinc-binding domain that is essential for M2-1 function, at the N terminus. To gain insight into its structural organization, M2-1 was produced as a recombinant protein in Escherichia coli and purified to >95% homogeneity by using a glutathione S-transferase (GST) tag. The GST-M2-1 fusion proteins were copurified with bacterial RNA, which could be eliminated by a high-salt wash. Circular dichroism analysis showed that M2-1 is largely α-helical. Chemical cross-linking, dynamic light scattering, sedimentation velocity, and electron microscopy analyses led to the conclusion that M2-1 forms a 5.4S tetramer of 89 kDa and ∼7.6 nm in diameter at micromolar concentrations. By using a series of deletion mutants, the oligomerization domain of M2-1 was mapped to a putative α-helix consisting of amino acid residues 32 to 63. When tested in an RSV minigenome replicon system using a luciferase gene as a reporter, an M2-1 deletion mutant lacking this region showed a significant reduction in RNA transcription compared to wild-type M2-1, indicating that M2-1 oligomerization is essential for the activity of the protein. We also show that the region encompassing amino acid residues 59 to 178 binds to P and RNA in a competitive manner that is independent of the phosphorylation status of M2-1.

scholarly journals Structural Insights Into the Design of Peptide-based Drug or Diagnostic Reagent Antagonizing SARS-COV-2

2020 ◽  
Author(s):  
junhao jiang ◽  
Ping Deng
Keyword(s):  
Amino Acid ◽  
Binding Affinity ◽  
Great Promise ◽  
Amino Acid Residues ◽  
Important Amino Acid ◽  
Amino Acid Mutations ◽  
Α Helix ◽  
New Interactions ◽  
Structural Insights ◽  
Blocking Capacity

Abstract Background Very limited drug and diagnostic reagents are currently available to tackle the emergence of SARS-CoV-2. However, recent findings about the structure of the complex about PD of ACE2 and RBD of SARS-CoV-2 spike protein hold great promise for the design of novel vaccines and peptides. To provide some suggestions for the design of peptide-based drug or diagnostic reagents antagonizing SARS-CoV-2, and describe the interactions between the receptor-binding domain of SARS-CoV-2 and PD domain of its receptor, ACE2. Methods Based on the PD-RBD crystal structure, the molecular interaction details of PD-RBD was contrasted. Results Amino acid mutations located in RBM of SARS-CoV result in the formation of new interactions between SARS-CoV-2 and α-helix 1, which can increase the binding affinity of SARS-CoV-2 to ACE2. It is confirmed that the α-helix 1 on ACE2 is the most important domain for binding spike glycoprotein of SARS-CoV-2, which can be used as a leading peptide for drug and diagnostic reagents development. Conclusion Based on the molecular-level characterization analysis between the PD and RBD, severe important amino acid residues (Q24, T27, K31, and H34) on α-helix 1 are proposed to mutate into increasing the binding affinity. Although the information provided in this study is predictive and based on no experimental evidence, it may provide useful suggestions for the experimental scientists to synthesize the proposed peptide and test their binding affinity and blocking capacity, and may be helpful for the understanding of SARS-CoV-2 entry.

scholarly journals Helix Formation in Preorganized β/γ-Peptide Foldamers: Hydrogen-Bond Analogy to the α-Helix without α-Amino Acid Residues

2010 ◽  
Vol 132 (23) ◽  
pp. 7868-7869 ◽  
Author(s):  
Li Guo ◽  
Aaron M. Almeida ◽  
Weicheng Zhang ◽  
Andrew G. Reidenbach ◽  
Soo Hyuk Choi ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Amino Acid ◽  
Amino Acid Residues ◽  
Helix Formation ◽  
Α Helix

scholarly journals Mutational Analysis of Xanthomonas Harpin HpaG Identifies a Key Functional Region That Elicits the Hypersensitive Response in Nonhost Plants

2004 ◽  
Vol 186 (18) ◽  
pp. 6239-6247 ◽  
Author(s):  
Jung-Gun Kim ◽  
Eunkyung Jeon ◽  
Jonghee Oh ◽  
Jae Sun Moon ◽  
Ingyu Hwang
Keyword(s):  
Amino Acid ◽  
Hypersensitive Response ◽  
Mutational Analysis ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Amino Acid Residues ◽  
Tobacco Plants ◽  
Functional Region ◽  
Amino Acid Peptide ◽  
Α Helix

ABSTRACT HpaG is a type III-secreted elicitor protein of Xanthomonas axonopodis pv. glycines. We have determined the critical amino acid residues important for hypersensitive response (HR) elicitation by random and site-directed mutagenesis of HpaG and its homolog XopA. A plasmid clone carrying hpaG was mutagenized by site-directed mutagenesis, hydroxylamine mutagenesis, and error-prone PCR. A total of 52 mutants were obtained, including 51 single missense mutants and 1 double missense mutant. The HR elicitation activity was abolished in the two missense mutants [HpaG(L50P) and HpaG(L43P/L50P)]. Seven single missense mutants showed reduced activity, and the HR elicitation activity of the rest of the mutants was similar to that of wild-type HpaG. Mutational and deletion analyses narrowed the region essential for elicitor activity to the 23-amino-acid peptide (H2N-NQGISEKQLDQLLTQLIMALLQQ-COOH). A synthetic peptide of this sequence possessed HR elicitor activity at the same concentration as the HpaG protein. This region has 78 and 74% homology with 23- and 27-amino-acid regions of the HrpW harpin domains, respectively, from Pseudomonas and Erwinia spp. The secondary structure of the peptide is predicted to be an α-helix, as is the HrpW region that is homologous to HpaG. The predicted α-helix of HpaG is probably critical for the elicitation of the HR in tobacco plants. In addition, mutagenesis of a xopA gene yielded two gain-of-function mutants: XopA(F48L) and XopA(F48L/M52L). These results indicate that the 12 amino acid residues between L39 and L50 of HpaG have critical roles in HR elicitation in tobacco plants.

Sign in / Sign up

Export Citation Format

Share Document