Effects of Selective Substitution of Cysteine Residues on the Conformational Properties of Chlorotoxin Explored by Molecular Dynamics Simulations.

Abstract:

:Chlorotoxin (CTX) is a 36⁻amino acid peptide with eight Cys residues that forms four disulfide bonds. It has high affinity for the glioma-specific chloride channel and matrix metalloprotease-2. Structural and binding properties of CTX analogs with various Cys residue substitutions with l-α-aminobutyric acid (Abu) have been previously reported. Using 4.2 µs molecular dynamics, we compared the conformational and essential space sampling of CTX and analogs with selective substitution of the Cys residues and associated disulfide bonds with either Abu or Ser. The native and substituted peptides maintained a high degree of α-helix propensity from residues 8 through 21, with the exception of substitution of the Cys⁵⁻Cys28 residues with Ser and the Cys16⁻Cys33 residues with Abu. In agreement with previous circular dichroism spectropolarimetry results, the C-terminal β-sheet content varied less from residues 25 through 29 and 32 through 36 and was well conserved in most analogs. The Cys16⁻Cys33 and Cys20⁻Cys35 disulfide-bonded residues appear to be required to maintain the αβ motif of CTX. Selective substitution with the hydrophilic Ser, may mitigate the destabilizing effect of Cys16⁻Cys33 substitution through the formation of an inter residue H-bond from Ser16:OγH to Ser33:OγH bridged by a water molecule. All peptides shared considerable sampled conformational space, which explains the retained receptor binding of the non-native analogs.

journal_name

Int J Mol Sci

authors

Gregory AJ,Voit-Ostricki L,Lovas S,Watts CR

doi

10.3390/ijms20061261

subject

Has Abstract

pub_date

2019-03-13 00:00:00

issue

6

issn

1422-0067

pii

ijms20061261

journal_volume

20

pub_type

杂志文章
  • Ruscogenin Attenuates Cerebral Ischemia-Induced Blood-Brain Barrier Dysfunction by Suppressing TXNIP/NLRP3 Inflammasome Activation and the MAPK Pathway.

    abstract::Ruscogenin, an important steroid sapogenin derived from Ophiopogon japonicus, has been shown to inhibit cerebral ischemic injury. However, its potential molecular action on blood-brain barrier (BBB) dysfunction after stroke remains unclear. This study aimed to investigate the effects of ruscogenin on BBB dysfunction a...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms17091418

    authors: Cao G,Jiang N,Hu Y,Zhang Y,Wang G,Yin M,Ma X,Zhou K,Qi J,Yu B,Kou J

    更新日期:2016-08-29 00:00:00

  • Slow Dissolution Kinetics of Model Peptide Fibrils.

    abstract::Understanding the kinetics of peptide self-assembly is important because of the involvement of peptide amyloid fibrils in several neurodegenerative diseases. In this paper, we have studied the dissolution kinetics of self-assembled model peptide fibrils after a dilution quench. Due to the low concentrations involved, ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21207671

    authors: Koder Hamid M,Rüter A,Kuczera S,Olsson U

    更新日期:2020-10-16 00:00:00

  • Synthetic Human TLR9-LRR11 Peptide Attenuates TLR9 Signaling by Binding to and thus Decreasing Internalization of CpG Oligodeoxynucleotides.

    abstract::Toll-like receptor (TLR) 9 is an endosomal receptor recognizing bacterial DNA/CpG-containing oligodeoxynucleotides (CpG ODN). Blocking CpG ODN/TLR9 activity represents a strategy for therapeutic prevention of immune system overactivation. Herein, we report that a synthetic peptide (SP) representing the leucine-rich re...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms17020242

    authors: Pan X,Li B,Kuang M,Liu X,Cen Y,Qin R,Ding G,Zheng J,Zhou H

    更新日期:2016-02-22 00:00:00

  • Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy.

    abstract::Diabetic cardiomyopathy (DCM) has emerged as a relevant cause of heart failure among the diabetic population. Defined as a cardiac dysfunction that develops in diabetic patients independently of other major cardiovascular risks factors, such as high blood pressure and coronary artery disease, the underlying cause of D...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20112833

    authors: Zamora M,Villena JA

    更新日期:2019-06-11 00:00:00

  • Analysis of Orthologous SECONDARY WALL-ASSOCIATED NAC DOMAIN1 (SND1) Promotor Activity in Herbaceous and Woody Angiosperms.

    abstract::SECONDARY WALL-ASSOCIATED NAC DOMAIN1 (SND1) is a master regulator of fibre secondary wall deposition in Arabidopsis thaliana (Arabidopsis), with homologs in other angiosperms and gymnosperms. However, it is poorly understood to what extent the fibre-specific regulation of the SND1 promoter, and that of its orthologs,...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20184623

    authors: Tonfack LB,Hussey SG,Veale A,Myburg AA,Mizrachi E

    更新日期:2019-09-18 00:00:00

  • Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China.

    abstract::Prior evidence indicates that homocysteine plays a role in the development of metabolic syndrome (MetS). Methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms are common genetic determinants of homocysteine levels. To investigate the associations of the MTHFR C67...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms151221687

    authors: Yang B,Fan S,Zhi X,Wang D,Li Y,Wang Y,Wang Y,Wei J,Zheng Q,Sun G

    更新日期:2014-11-25 00:00:00

  • Comparative Study of Interactions between Human cGAS and Inhibitors: Insights from Molecular Dynamics and MM/PBSA Studies.

    abstract::Recent studies have identified cyclic GMP-AMP synthase (cGAS) as an important target for treating autoimmune diseases, and several inhibitors of human cGAS (hcGAS) and their structures in complexation with hcGAS have been reported. However, the mechanisms via which these inhibitors interact with hcGAS are not complete...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms22031164

    authors: Wang X,Li W

    更新日期:2021-01-25 00:00:00

  • Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese.

    abstract::Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. K...

    journal_title:International journal of molecular sciences

    pub_type: 临床试验,杂志文章

    doi:10.3390/ijms18081775

    authors: Wang CM,Wang SH,Jan Wu YJ,Lin JC,Wu J,Chen JY

    更新日期:2017-08-16 00:00:00

  • Pulmonary Arterial Hypertension Due to NPR-C Mutation: A Novel Paradigm for Normal and Pathologic Remodeling?

    abstract::Idiopathic Pulmonary Arterial Hypertension (IPAH) is a deadly and disabling disease characterized by severe vascular remodeling of small pulmonary vessels by fibroblasts, myofibroblasts and vascular smooth muscle cell proliferation. Recent studies suggest that the Natriuretic Peptide Clearance Receptor (NPR-C) signali...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20123063

    authors: Egom EE

    更新日期:2019-06-22 00:00:00

  • Review on Bifidobacterium bifidum BGN4: Functionality and Nutraceutical Applications as a Probiotic Microorganism.

    abstract::Bifidobacterium bifidum BGN4 is a probiotic strain that has been used as a major ingredient to produce nutraceutical products and as a dairy starter since 2000. The various bio-functional effects and potential for industrial application of B. bifidum BGN4 has been characterized and proven by in vitro (i.e., phytochemi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms17091544

    authors: Ku S,Park MS,Ji GE,You HJ

    更新日期:2016-09-14 00:00:00

  • Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues.

    abstract::Rheumatoid arthritis (RA) is a polygenic and multifactorial syndrome. Many complex immunological and genetic interactions are involved in the final outcome of the clinical disease. Autoantibodies (rheumatoid factors, anti-citrullinated peptide/protein antibodies) are present in RA patients' sera for a long time before...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms19030677

    authors: Nandakumar KS

    更新日期:2018-02-28 00:00:00

  • The Essential Role of Pin1 via NF-κB Signaling in Vascular Inflammation and Atherosclerosis in ApoE-/- Mice.

    abstract::Atherosclerosis, as a chronic inflammatory disease, is the major underlying cause of death worldwide. However, the mechanisms that underlie the inflammatory process are not completely understood. Prolyl-isomerase-1 (Pin1), as a unique peptidyl-prolyl isomerase, plays an important role in inflammation and endothelial d...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms18030644

    authors: Liu M,Yu P,Jiang H,Yang X,Zhao J,Zou Y,Ge J

    更新日期:2017-03-16 00:00:00

  • Effects of Mutations on Structure-Function Relationships of Matrix Metalloproteinase-1.

    abstract::Matrix metalloproteinase-1 (MMP-1) is one of the most widely studied enzymes involved in collagen degradation. Mutations of specific residues in the MMP-1 hemopexin-like (HPX) domain have been shown to modulate activity of the MMP-1 catalytic (CAT) domain. In order to reveal the structural and conformational effects o...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms17101727

    authors: Singh W,Fields GB,Christov CZ,Karabencheva-Christova TG

    更新日期:2016-10-14 00:00:00

  • Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening.

    abstract::Adlay (Coix larchryma-jobi L.) was the commonly used Traditional Chinese Medicine (TCM) with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopep...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms17122099

    authors: Qiao L,Li B,Chen Y,Li L,Chen X,Wang L,Lu F,Luo G,Li G,Zhang Y

    更新日期:2016-12-14 00:00:00

  • Dissecting the Seed Maturation and Germination Processes in the Non-Orthodox Quercus ilex Species Based on Protein Signatures as Revealed by 2-DE Coupled to MALDI-TOF/TOF Proteomics Strategy.

    abstract::Unlike orthodox species, seed recalcitrance is poorly understood, especially at the molecular level. In this regard, seed maturation and germination were studied in the non-orthodox Quercus ilex by using a proteomics strategy based on two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption ioni...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21144870

    authors: Sghaier-Hammami B,B M Hammami S,Baazaoui N,Gómez-Díaz C,Jorrín-Novo JV

    更新日期:2020-07-09 00:00:00

  • Inhibition of acetylcholinesterase modulates NMDA receptor antagonist mediated alterations in the developing brain.

    abstract::Exposure to N-methyl-d-aspartate (NMDA) receptor antagonists has been demonstrated to induce neurodegeneration in newborn rats. However, in clinical practice the use of NMDA receptor antagonists as anesthetics and sedatives cannot always be avoided. The present study investigated the effect of the indirect cholinergic...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms15033784

    authors: Bendix I,Serdar M,Herz J,von Haefen C,Nasser F,Rohrer B,Endesfelder S,Felderhoff-Mueser U,Spies CD,Sifringer M

    更新日期:2014-03-03 00:00:00

  • Myoblast Migration and Directional Persistence Affected by Syndecan-4-Mediated Tiam-1 Expression and Distribution.

    abstract::Skeletal muscle is constantly renewed in response to injury, exercise, or muscle diseases. Muscle stem cells, also known as satellite cells, are stimulated by local damage to proliferate extensively and form myoblasts that then migrate, differentiate, and fuse to form muscle fibers. The transmembrane heparan sulfate p...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21030823

    authors: Becsky D,Gyulai-Nagy S,Balind A,Horvath P,Dux L,Keller-Pinter A

    更新日期:2020-01-27 00:00:00

  • Leucine-Rich Repeat Kinase 2 Controls Inflammatory Cytokines Production through NF-κB Phosphorylation and Antigen Presentation in Bone Marrow-Derived Dendritic Cells.

    abstract::Leucine-rich repeat kinase 2 (LRRK2) is the causal molecule of familial Parkinson's disease. Although the characteristics of LRRK2 have gradually been revealed, its true physiological functions remain unknown. LRRK2 is highly expressed in immune cells such as B2 cells and macrophages, suggesting that it plays importan...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21051890

    authors: Kubo M,Nagashima R,Kurihara M,Kawakami F,Maekawa T,Eshima K,Ohta E,Kato H,Obata F

    更新日期:2020-03-10 00:00:00

  • The Na/K-ATPase Signaling: From Specific Ligands to General Reactive Oxygen Species.

    abstract::The signaling function of the Na/K-ATPase has been established for 20 years and is widely accepted in the field, with many excellent reports and reviews not cited here. Even though there is debate about the underlying mechanism, the signaling function is unquestioned. This short review looks back at the evolution of N...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms19092600

    authors: Pratt RD,Brickman CR,Cottrill CL,Shapiro JI,Liu J

    更新日期:2018-09-01 00:00:00

  • Hepatocellular Carcinoma-The Influence of Immunoanatomy and the Role of Immunotherapy.

    abstract::Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Most patients are diagnosed with advanced disease, limiting their options for treatment. While current treatments are adequate for lower staged disease, available systemic treatments are limited, with marginal benefi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms21186757

    authors: Patel K,Lamm R,Altshuler P,Dang H,Shah AP

    更新日期:2020-09-15 00:00:00

  • Mitochondrial Carriers for Aspartate, Glutamate and Other Amino Acids: A Review.

    abstract::Members of the mitochondrial carrier (MC) protein family transport various molecules across the mitochondrial inner membrane to interlink steps of metabolic pathways and biochemical processes that take place in different compartments; i.e., are localized partly inside and outside the mitochondrial matrix. MC substrate...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms20184456

    authors: Monné M,Vozza A,Lasorsa FM,Porcelli V,Palmieri F

    更新日期:2019-09-10 00:00:00

  • Calcium ions regulate K⁺ uptake into brain mitochondria: the evidence for a novel potassium channel.

    abstract::The mitochondrial response to changes of cytosolic calcium concentration has a strong impact on neuronal cell metabolism and viability. We observed that Ca(2+) additions to isolated rat brain mitochondria induced in potassium ion containing media a mitochondrial membrane potential depolarization and an accompanying in...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms10031104

    authors: Skalska J,Bednarczyk P,Piwońska M,Kulawiak B,Wilczynski G,Dołowy K,Kudin AP,Kunz WS,Szewczyk A

    更新日期:2009-03-01 00:00:00

  • EGFR and EGFRvIII Promote Angiogenesis and Cell Invasion in Glioblastoma: Combination Therapies for an Effective Treatment.

    abstract::Epidermal growth factor receptor (EGFR) and the mutant EGFRvIII are major focal points in current concepts of targeted cancer therapy for glioblastoma multiforme (GBM), the most malignant primary brain tumor. The receptors participate in the key processes of tumor cell invasion and tumor-related angiogenesis and their...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms18061295

    authors: Keller S,Schmidt MHH

    更新日期:2017-06-18 00:00:00

  • Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study of Plasmodium falciparum Hsp70s.

    abstract::Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malar...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20225574

    authors: Amusengeri A,Astl L,Lobb K,Verkhivker GM,Tastan Bishop Ö

    更新日期:2019-11-08 00:00:00

  • Identification and Comparative Analysis of CBS Domain-Containing Proteins in Soybean (Glycine max) and the Primary Function of GmCBS21 in Enhanced Tolerance to Low Nitrogen Stress.

    abstract::Nitrogen is an important macronutrient required for plant growth, and is a limiting factor for crop productivity. Improving the nitrogen use efficiency (NUE) is therefore crucial. At present, the NUE mechanism is unclear and information on the genes associated with NUE in soybeans is lacking. cystathionine beta syntha...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms17050620

    authors: Hao Q,Shang W,Zhang C,Chen H,Chen L,Yuan S,Chen S,Zhang X,Zhou X

    更新日期:2016-04-26 00:00:00

  • Plumbagin Suppresses α-MSH-Induced Melanogenesis in B16F10 Mouse Melanoma Cells by Inhibiting Tyrosinase Activity.

    abstract::Recent studies have shown that plumbagin has anti-inflammatory, anti-allergic, antibacterial, and anti-cancer activities; however, it has not yet been shown whether plumbagin suppresses alpha-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis to prevent hyperpigmentation. In this study, we demonstrated t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms18020320

    authors: Oh TI,Yun JM,Park EJ,Kim YS,Lee YM,Lim JH

    更新日期:2017-02-03 00:00:00

  • Unique Gut Microbiome Signatures Depict Diet-Versus Genetically Induced Obesity in Mice.

    abstract::The gut microbiome plays an important role in obesity and Type 2 diabetes (T2D); however, it remains unclear whether the gut microbiome could clarify the dietary versus genetic origin of these ailments. Moreover, studies examining the gut microbiome in diet- versus genetically induced obesity/T2D in the same experimen...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21103434

    authors: Nagpal R,Mishra SP,Yadav H

    更新日期:2020-05-13 00:00:00

  • Regulatory miRNAs in Colorectal Carcinogenesis and Metastasis.

    abstract::Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in car...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审

    doi:10.3390/ijms18040890

    authors: Guo Y,Bao Y,Yang W

    更新日期:2017-04-22 00:00:00

  • LGM2605 Reduces Space Radiation-Induced NLRP3 Inflammasome Activation and Damage in In Vitro Lung Vascular Networks.

    abstract::Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation risks to a...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms20010176

    authors: Chatterjee S,Pietrofesa RA,Park K,Tao JQ,Carabe-Fernandez A,Berman AT,Koumenis C,Sielecki T,Christofidou-Solomidou M

    更新日期:2019-01-05 00:00:00

  • Bactericidal and Bioresorbable Calcium Phosphate Cements Fabricated by Silver-Containing Tricalcium Phosphate Microspheres.

    abstract::Bacterial adhesion to the calcium phosphate surface is a serious problem in surgery. To prevent bacterial infection, the development of calcium-phosphate cements (CPCs) with bactericidal properties is indispensable. The aim of this study was to fabricate antibacterial CPCs and evaluate their biological properties. Sil...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章

    doi:10.3390/ijms21113745

    authors: Honda M,Kawanobe Y,Nagata K,Ishii K,Matsumoto M,Aizawa M

    更新日期:2020-05-26 00:00:00