scholarly journals Correlation Analysis for Protein Evolutionary Family Based on Amino Acid Position Mutations and Application in PDZ Domain

PLoS ONE ◽  
2010 ◽  
Vol 5 (10) ◽  
pp. e13207 ◽  
Author(s):  
Qi-Shi Du ◽  
Cheng-Hua Wang ◽  
Si-Ming Liao ◽  
Ri-Bo Huang
Keyword(s):  
Amino Acid ◽  
Correlation Analysis ◽  
Pdz Domain ◽  
Amino Acid Position ◽  
Family Based

A Novel Amino Acid Sequence-based Computational Approach to Predicting Cell-penetrating Peptides

2019 ◽  
Vol 15 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Jihui Tang ◽  
Jie Ning ◽  
Xiaoyan Liu ◽  
Baoming Wu ◽  
Rongfeng Hu
Keyword(s):  
Machine Learning ◽  
Amino Acid ◽  
Amino Acid Position ◽  
Cell Penetrating Peptides ◽  
Support Vector ◽  
Cell Penetration ◽  
Drug Candidates ◽  
Machine Learning Model ◽  
Cell Penetrating ◽  
Novel Method

<P>Introduction: Machine Learning is a useful tool for the prediction of cell-penetration compounds as drug candidates. </P><P> Materials and Methods: In this study, we developed a novel method for predicting Cell-Penetrating Peptides (CPPs) membrane penetrating capability. For this, we used orthogonal encoding to encode amino acid and each amino acid position as one variable. Then a software of IBM spss modeler and a dataset including 533 CPPs, were used for model screening. </P><P> Results: The results indicated that the machine learning model of Support Vector Machine (SVM) was suitable for predicting membrane penetrating capability. For improvement, the three CPPs with the most longer lengths were used to predict CPPs. The penetration capability can be predicted with an accuracy of close to 95%. </P><P> Conclusion: All the results indicated that by using amino acid position as a variable can be a perspective method for predicting CPPs membrane penetrating capability.</P>

scholarly journals Identification of separate domains in the adenovirus E1A gene for immortalization activity and the activation of virus early genes.

1986 ◽  
Vol 6 (10) ◽  
pp. 3470-3480 ◽  
Author(s):  
E Moran ◽  
B Zerler ◽  
T M Harrison ◽  
M B Mathews
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Point Mutations ◽  
Apparent Molecular Weight ◽  
Amino Acid Position ◽  
Cysteine Residue ◽  
Transformation Function ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
E1a Gene

The transformation and early adenovirus gene transactivation functions of the E1A region were analyzed with deletion and point mutations. Deletion of amino acids from position 86 through 120 had little effect on the lytic or transforming functions of the E1A products, while deletion of amino acids from position 121 through 150 significantly impaired both functions. The sensitivity of the transformation function to alterations in the region from amino acid position 121 to 150 was further indicated by the impairment of transforming activity resulting from single amino acid substitutions at positions 124 and 135. Interestingly, conversion of a cysteine residue at position 124 to glycine severely impaired the transformation function without affecting the early adenovirus gene activating functions. Single amino acid substitutions in a different region of the E1A gene had the converse effect. All the mutants produced polypeptides of sufficient stability to be detected by Western immunoblot analysis. The single amino acid substitutions at positions 124 and 135, although impairing the transformation functions, did not detectably alter the formation of the higher-apparent-molecular-weight forms of the E1A products.

The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction

2003 ◽  
Vol 284 (3) ◽  
pp. C667-C673 ◽  
Author(s):  
Alexander Pushkin ◽  
Natalia Abuladze ◽  
Debra Newman ◽  
Vladimir Muronets ◽  
Pejvak Sassani ◽  
...  
Keyword(s):  
Amino Acid ◽  
Proton Pump ◽  
Rat Kidney ◽  
Pdz Domain ◽  
Intercalated Cells ◽  
Regulatory Factor ◽  
Atpase Subunit ◽  
Sodium Bicarbonate Cotransporter ◽  
Terminal Amino ◽  
Vacuolar Proton Pump

The electroneutral sodium bicarbonate cotransporter 3 (NBC3) coimmunoprecipitates from renal lysates with the vacuolar H+-ATPase. In renal type A and B intercalated cells, NBC3 colocalizes with the vacuolar H+-ATPase. The involvement of the COOH termini of NBC3 and the 56-kDa subunit of the proton pump in the interaction of these proteins was investigated. The intact and modified COOH termini of NBC3 and the 56-kDa subunit of the proton pump were synthesized, coupled to Sepharose beads, and used to pull down kidney membrane proteins. Both the 56- and the 70-kDa subunits of the proton pump, as well as a PDZ domain containing protein Na+/H+ exchanger regulatory factor 1 (NHERF-1), were bound to the intact 18 amino acid NBC3 COOH terminus. A peptide truncated by five COOH-terminal amino acids did not bind these proteins. Replacement of the COOH-terminal leucine with glycine blocked binding of both the proton pump subunits but did not affect binding of NHERF-1. The 18 amino acid COOH terminus of the 56-kDa subunit of the proton pump bound NHERF-1 and NBC3, but the truncated and modified peptide did not. A complex of NBC3, the 56-kDa subunit of the proton pump, and NHERF-1 was identified in rat kidney. The data indicate that the COOH termini of NBC3 and the 56-kDa subunit of the vacuolar proton pump are PDZ-interacting motifs that are necessary for the interaction of these proteins. NHERF-1 is involved in the interaction of NBC3 and the vacuolar proton pump.

scholarly journals T-Cell Response to Human Papillomavirus Type 58 L1, E6, and E7 Peptides in Women with Cleared Infection, Cervical Intraepithelial Neoplasia, or Invasive Cancer

2010 ◽  
Vol 17 (9) ◽  
pp. 1315-1321 ◽  
Author(s):  
Paul K. S. Chan ◽  
Shih-Jen Liu ◽  
T. H. Cheung ◽  
Winnie Yeo ◽  
S. M. Ngai ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Amino Acid ◽  
T Cell ◽  
Cell Response ◽  
Positive Response ◽  
Intraepithelial Neoplasia ◽  
Amino Acid Position ◽  
T Cell Response ◽  
Ifn Γ ◽  
E6 And E7

ABSTRACT Human papillomavirus type 58 (HPV-58) exists in a relatively high prevalence in certain parts of the world, including East Asia. This study examined the T-cell response to HPV-58 L1, E6, and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3, or invasive cervical cancer (ICC). Peptides found to be reactive in the in vitro peptide binding assay or mouse-stimulating study were tested with a gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay to detect peptide-specific responses from the peripheral blood mononuclear cells (PBMC) collected from 91 HPV-58-infected women (32 with cleared infection, 16 CIN2, 15 CIN3, and 28 ICC). Four HLA-A11-restricted HPV-58 L1 peptides, located at amino acid positions 296 to 304, 327 to 335, 101 to 109, and 469 to 477, showed positive IFN-γ ELISPOT results and were mainly from women with cleared infection. Two HLA-A11-restricted E6 peptides (amino acid positions 64 to 72 and 94 to 102) and three HLA-A11-restricted E7 peptides (amino acid positions 78 to 86, 74 to 82, and 88 to 96) showed a positive response. A response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA-A2-restricted E6 peptide, located at amino acid position 99 to 107, elicited a positive response in two CIN2 subjects. One HLA-A24-restricted L1 peptide, located at amino acid position 468 to 476, also elicited a positive response in two CIN2 subjects. In summary, this study has identified a few immunogenic epitopes for HPV-58 E6 and E7 proteins. It is worthwhile to further investigate whether responses to these epitopes have a role in clearing an established cervical lesion.

scholarly journals Impact of evolutionary selection on dynamic behavior of MCAK protein

2020 ◽  
Author(s):  
Shiwani Limbu
Keyword(s):  
Amino Acid ◽  
Amino Acid Position ◽  
Coding Region ◽  
Microtubule Depolymerization ◽  
Protein Coding ◽  
Microtubule Binding ◽  
Evolutionary Selection ◽  
Family Protein ◽  
Α Helix

AbstractKinesins of class 13 (kinesin-13s), also known as KinI family proteins, are non-motile microtubule binding kinesin proteins. Mitotic centromere-associated kinesin (MCAK), a member of KinI family protein, diffuses along the microtubule and plays a key role in microtubule depolymerization. Here we have demonstrated the role of evolutionary selection in MCAK protein coding region in regulating its dynamics associated with microtubule binding and stability. Our results indicate that evolutionary selection within MCAK motor domain at amino acid position 440 in carnivora and artiodactyla order results in significant change in the dynamics of α – helix and loop 11, indicating its likely impact on changing the microtubule binding and depolymerization process. Furthermore, evolutionary selections at amino acid position 600, 617 and 698 are likely to affect MCAK stability. A deeper understanding of evolutionary selections in MCAK can reveal the mechanism associated with change in microtubule dynamics within eutherian mammals.

scholarly journals Fine mapping MHC associations in Graves’ disease and its clinical subtypes in Han Chinese

2018 ◽  
Vol 55 (10) ◽  
pp. 685-692 ◽  
Author(s):  
Xun Chu ◽  
Minjun Yang ◽  
Zhen-Ju Song ◽  
Yan Dong ◽  
Chong Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Mechanisms ◽  
Amino Acid Level ◽  
Antithyroid Drug ◽  
Amino Acid Position ◽  
Thyroid Stimulating Hormone ◽  
Han Chinese ◽  
Graves Disease ◽  
Hla Genes ◽  
Antithyroid Drug Therapy

BackgroundThe classical human leucocyte antigen (HLA) genes were the most important genetic determinant for Graves’ disease (GD). The aim of the study was to fine map causal variants of the HLA genes.MethodsWe applied imputation with a Pan-Asian HLA reference panel to thoroughly investigate themajor histocompatibility complex (MHC) associations with GD down to the amino acid level of classical HLA genes in 1468 patients with GD and 1490 controls of Han Chinese.ResultsThe strongest finding across the HLA genes was the association with HLA-DPβ1 position 205 (Pomnibus=2.48×10−33). HLA-DPA1*02:02 was the strongest association among the classical HLA alleles, which was in perfect linkage disequilibrium with HLA-DPα1 residue Met11 (OR=1.90, Pbinary=1.76×10−31). Applying stepwise conditional analysis, we identified amino acid position 205 in HLA-DPβ1, position 66 and 99 in HLA-B and position 28 in HLA-DRβ1 explain majority of the MHC association to GD risk. We further evaluated risk of two clinical subtypes of GD, namely persistent thyroid stimulating hormone receptor antibody -positive (pTRAb+) group and ‘non-persistent TRAb positive’ (pTRAb−) group after antithyroid drug therapy. We found that HLA-B residues Lys66-Arg69-Val76 could drive pTRAb− GD risk alone, while HLA-DPβ1 position 205, HLA-B position 69 and 199 and HLA-DRβ1 position 28 drive pTRAb+ GD risk. The risk heterogeneity between pTRAb+ and pTRAb− GD might be driven by HLA-DPα1 Met11.ConclusionsFour amino acid positions could account for the associations of MHC with GD in Han Chinese. These distinct HLA association patterns indicated the two subtypes have distinct molecular mechanisms of pathogenesis.

Abstract 901: Effects of Bucindolol on Cardiovascular Mortality and Morbidity are Determined by the Beta-1 389 Arg/Gly Receptor Polymorphism

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Michel White ◽  
Peter Carson ◽  
Inder S Anand ◽  
Stephen S Gottlieb ◽  
JoAnn Lindenfeld ◽  
...  
Keyword(s):  
Heart Failure ◽  
Amino Acid ◽  
Cardiovascular Mortality ◽  
Nyha Class ◽  
Total Mortality ◽  
Chronic Administration ◽  
Amino Acid Position ◽  
Class Iii ◽  
Mortality And Morbidity ◽  
The Impact

Introduction: Bucindolol is a nonselective beta-adrenergic blocker with potent sympatholytic properties. The Beta-blocker Evaluation of Survival Trial (BEST) reported that the administration of bucindolol resulted in a nonsignificant decrease in total mortality (HR = 0.89 (0.78, 1.02), unadjusted p=0.10) in patients with advanced, NYHA Class III-IV heart failure (HF). Recent observations from that trial also reported that the amino acid arginine (Arg/Arg) or glycine (any Gly) in position 389 of the beta-1 receptor plays a significant role on the clinical response to bucindolol. The impact of bucindolol on cardiovascular mortality and morbidity (cardiovascular hospitalizations) has been incompletely investigated, because hospitalizations had been evaluated from case report forms (CRFs) only, and never adjudicated by the endpoints committee (EPC). Methods: The BEST data base consists of 2708 patients with a mean follow-up of 2.0 years. Cardiovascular (CV) mortality and hospitalizations have now been evaluated by EPC, which further subclassified total hospitalizations into cardiovascular (CV) and those due to worsening heart failure (HF). The impacts of Arg or Gly encoded at amino acid position 389 on endpoints were further investigated in the 1040 patient substudy. Results: Time to event results for adjudicated CV endpoints are presented below. Conclusions: Chronic administration of bucindolol results in a significant reduction in cardiovascular hospitalizations and mortality. Effects on either are strikingly beta-1 389 Arg/Gly specific, with the higher functioning, Arg/Arg version of the receptor associated with large treatment effects and Gly carriers exhibiting little or no evidence of efficacy. Genetic targeting of the β 1 -ΑR 389 polymorphism may improve the clinical responses to bucindolol for CV mortality and morbidity.

scholarly journals A Naturally Occurring Rgg Variant in Serotype M3 Streptococcus pyogenes Does Not Activate speB Expression Due to Altered Specificity of DNA Binding

2009 ◽  
Vol 77 (12) ◽  
pp. 5411-5417 ◽  
Author(s):  
Kyle V. Kappeler ◽  
Srivishnupriya Anbalagan ◽  
Alexander V. Dmitriev ◽  
Emily J. McDowell ◽  
Melody N. Neely ◽  
...  
Keyword(s):  
Amino Acid ◽  
Streptococcus Pyogenes ◽  
Murine Model ◽  
Cysteine Protease ◽  
Phenotypic Diversity ◽  
Transcriptional Regulator ◽  
Amino Acid Position ◽  
Invasive Disease ◽  
Naturally Occurring

ABSTRACT The transcriptional regulator Rgg of Streptococcus pyogenes is essential for expression of the secreted cysteine protease SpeB. Although all isolates of S. pyogenes possess the speB gene, not all of them produce the protein in vitro. In a murine model of infection, the absence of SpeB production is associated with invasive disease. We speculated that naturally occurring mutations in rgg, which would also abrogate SpeB production, may be present in invasive isolates of S. pyogenes. Examination of the inferred Rgg sequences available in public databases revealed that the rgg gene in strain MGAS315 (a serotype M3 strain associated with invasive disease) encodes a proline at amino acid position 103 (Rgg103P); in contrast, all other strains encode a serine at this position (Rgg103S). A caseinolytic assay and Western blotting indicated that strain MGAS315 does not produce SpeB in vitro. Gene-swapping experiments showed that the rgg gene of MGAS315 is solely responsible for the lack of SpeB expression. In contrast to Rgg103S, Rgg103P does not bind to the speB promoter in gel shift assays, which correlates with a lack of speB expression. Despite its inability to activate speB expression, Rgg103P retains the ability to bind to DNA upstream of norA and to influence its expression. Overall, this study illustrates how variation at the rgg locus may contribute to the phenotypic diversity of S. pyogenes.

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