Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms

1996 ◽  
Vol 76 (3) ◽  
pp. 887-926 ◽  
Author(s):  
H. A. Fozzard ◽  
D. A. Hanck
Keyword(s):  
Amino Acid ◽  
Three Dimensional ◽  
Point Mutations ◽  
Amino Acid Sequences ◽  
Na Channel ◽  
Na Channels ◽  
Voltage Dependent ◽  
And Function ◽  
Relationship Of ◽  
The Relationship

Cardiac and nerve Na channels have broadly similar functional properties and amino acid sequences, but they demonstrate specific differences in gating, permeation, ionic block, modulation, and pharmacology. Resolution of three-dimensional structures of Na channels is unlikely in the near future, but a number of amino acid sequences from a variety of species and isoforms are known so that channel differences can be exploited to gain insight into the relationship of structure to function. The combination of molecular biology to create chimeras and channels with point mutations and high-resolution electrophysiological techniques to study function encourage the idea that predictions of structure from function are possible. With the goal of understanding the special properties of the cardiac Na channel, this review examines the structural (sequence) similarities between the cardiac and nerve channels and considers what is known about the relationship of structure to function for voltage-dependent Na channels in general and for the cardiac Na channels in particular.

Three-Dimensional Modelling of Honeybee Venom Allergenic Proteases: Relation to Allergenicity

2011 ◽  
Vol 66 (5-6) ◽  
pp. 305-312 ◽  
Author(s):  
Dessislava Georgieva ◽  
Kerstin Greunke ◽  
Raghuvir K. Arni ◽  
Christian Betzel
Keyword(s):  
Amino Acid ◽  
Serine Proteases ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Honeybee Venom ◽  
Linker Peptide ◽  
Cub Domain ◽  
And Function ◽  
Substrate Binding Sites ◽  
Related Proteins

Api SI and Api SII are serine proteases of the honeybee venom containing allergenic determinants. Each protease consists of two structural modules: an N-terminal CUB (Api SI) or a clip domain (Api SII) and a C-terminal serine protease-like (SPL) domain. Both domains are connected with a linker peptide. The knowledge about the structure and function of Api SI and Api SII is limited mainly to their amino acid sequences. We constructed 3-D models of the two proteases using their amino acid sequences and crystallographic coordinates of related proteins. The models of the SPL domains were built using the structure of the prophenoloxidase-activating factor (PPAF)-II as a template. For modelling of the Api SI CUB domain the coordinates of porcine spermadhesin PSP-I were used. The models revealed the catalytic and substrate-binding sites and the negatively charged residue responsible for the trypsin-like activity. IgE-binding and antigenic sites in the two allergens were predicted using the models and programs based on the structure of known epitopes. Api SI and Api SII show structural and functional similarity to the members of the PPAF-II family. Most probably, they are part of the defence system of Apis mellifera

Functional discrimination of sea anemone neurotoxins using 3D-plotting

2009 ◽  
Vol 4 (1) ◽  
pp. 41-49
Author(s):  
Ludis Morales ◽  
Orlando Acevedo ◽  
María Martínez ◽  
Dmitry Gokhman ◽  
Carlos Corredor
Keyword(s):  
Amino Acid ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Sea Anemone ◽  
Amino Acid Sequences ◽  
Peptide Sequence ◽  
Sea Anemones ◽  
Functional Relationships ◽  
Voltage Dependent ◽  
Three Dimensional Space

AbstractOne of the most important goals in structural biology is the identification of functional relationships among the structure of proteins and peptides. The purpose of this study was to (1) generate a model based on theoretical and computational considerations among amino acid sequences within select neurotoxin peptides, and (2) compare the relationship these values have to the various toxins tested. We employed isolated neurotoxins from sea anemones with established specific potential to act on voltage-dependent sodium and potassium channel activity as our model. Values were assigned to each amino acid in the peptide sequence of the neurotoxins tested using the Number of Lareo and Acevedo algorithm (NULA). Once the NULA number was obtained, it was then plotted using three dimensional space coordinates. The results of this study allow us to report, for the first time, that there is a different numerical and functional relationship between the sequences of amino acids from sea anemone neurotoxins, and the resulting numerical relationship for each peptide, or NULA number, has a unique location in three-dimensional space.

Phylogeny of pentatomomorphan bugs (Hemiptera-Heteroptera: Pentatomomorpha) based on six Hox gene fragments

Zootaxa ◽  
2011 ◽  
Vol 2888 (1) ◽  
pp. 57 ◽  
Author(s):  
XIAOXUAN TIAN ◽  
QIANG XIE ◽  
MIN LI ◽  
CUIQING GAO ◽  
YING CUI ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Amino Acid ◽  
Bayesian Methods ◽  
Hox Genes ◽  
Amino Acid Sequences ◽  
Morphological Data ◽  
Hox Gene ◽  
True Bugs ◽  
Relationship Of ◽  
The Relationship

Pentatomomorpha is one of the most diversified infraorders of the true bugs (Insecta: Hemiptera: Heteroptera). The phylogenetic relationships among superfamilies within this infraorder are still in dispute. In this study, 31 species representing 26 pentatomomorphan and four cimicomorphan putative families were chosen, and six Hox gene fragments with as many as 4 kilobases for each representative were analyzed to reconstruct the phylogeny of the Pentatomomorpha. The (Homeotic) Hox gene family is a group of nuclear genes, which is considered to determine animal segmentation. The combined nucleotide and amino acid sequences were used separately as two data matrices, and analyzed by employing maximum likelihood and Bayesian methods. Results strongly support the monophyly of Trichophora and the superfamilies Pentatomoidea, Lygaeoidea, Coreoidea, and Pyrrhocoroidea. The relationship of (Aradoidea + (Pentatomoidea + (Lygaeoidea + (Coreoidea + Pyrrhocoroidea)))) was mostly congruent with previous results based on the morphological data. Our results suggested that the Hox genes could be used as novel molecular markers for phylogenetic research on the Pentatomomorpha and other insects.

scholarly journals Mutation and Phylogenetic Analysis of Spike Glycoprotein of Indonesian Isolates of Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2)

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Shabarni Gaffar ◽  
◽  
Syifa Al Fauziah Rahmani ◽  
Ari Hardianto
Keyword(s):  
Amino Acid ◽  
Phylogenetic Trees ◽  
Point Mutations ◽  
Surface Protein ◽  
Amino Acid Sequences ◽  
Effective Vaccine ◽  
Neighbor Joining ◽  
Multiple Sequence ◽  
Spike Gene ◽  
Relationship Of

Coronavirus disease-2019 (COVID-19) is an infectious acute respiratory disease caused by SARS-CoV-2. The protein that plays a role in the entry of SARS-CoV-2 into human cells is the surface protein, or the Spike, which is thought to be the effective vaccine target to prevent SARS-CoV-2 infection. Until December 2020, Indonesia has reported 106 SARS-CoV-2 genome sequences identified from COVID-19 positive patients. The purpose of this study was to analyze the phylogenetic relationship of the Spike protein of the Indonesian isolates of SARS-CoV-2 Indonesian, as well as the virus mutations and their effects on changes in the amino acid. The 106 Indonesian SARS-CoV-2 genomes were downloaded from GISAID and the Spike nucleotide and amino acid sequences were analyzed by multiple sequence alignment (MSA) and mutation analysis using the ClustalW method. Phylogenetic trees were created using the Neighbor-Joining method in MEGA-X software. The results showed that 30 of the 106 Indonesian isolate SARS-CoV-2 Spike were 100% identical to the Wuhan-Hu-1, while the remaining 76 had experienced mutations at 1-4 sites. There were 43-point mutations in the Spike gene, 27 of which led to amino acid changes and four had not been reported in other countries. The global mutation D614G was found in 60 Indonesian isolates , of which West Java was the province with the most reports. The phylogenetic of Spike showed that the Indonesian samples have been divided into several branches that are far from Wuhan-Hu-1. This study indicates the possibility of differences in the protein structure of Indonesian isolate SARS-CoV-2 Spike that need to be further studied to manufacture a vaccine against the Indonesian strain of SARS-CoV-2.

scholarly journals Short communication: The diversity of ureolytic bacteria isolated from limestone in East Java, Indonesia based on amino acid sequences encoded by ureC

2019 ◽  
Vol 20 (8) ◽  
Author(s):  
ENNY ZULAIKA ◽  
M. A. PRIO UTOMO ◽  
N. HIDAYATUL ALAMI ◽  
N. DWIANITA KUSWYTASARI ◽  
MAYA SHOVITRI ◽  
...  
Keyword(s):  
Amino Acid ◽  
Short Communication ◽  
Amino Acid Sequences ◽  
Local Alignment ◽  
Lysinibacillus Sphaericus ◽  
Urease Enzyme ◽  
Search Tool ◽  
And Function ◽  
Relationship Of ◽  
Ureolytic Bacteria

Abstract. Zulaika E, Utomo MAP, Alami NH, Kuswytasari ND, Shovitri M, Bayuaji R, Prasetyo EN. 2019. Short communication: The diversity of ureolytic bacteria isolated from limestone in East Java, Indonesia based on amino acid sequences encoded by ureC. Biodiversitas 20: 2316-2320. Ureolytic bacteria isolated from limestone are capable to produce urease enzyme which can breaks down urea into carbonate (CO32), has been utilized for various building material bioremediation and restoration. In this present study, we figured out the diversity and genetic relationship of α sub-unit ureC gene among six ureolytic bacteria (JA1, JB2, JB3, JA4, AK4, and SU1) which were isolated from limestone area in East Java province. PCR was conducted to detect the gene which encoded active site of urease, ureC. Followed by sequences translation using BLAST-X (Basic Local Alignment Search Tool) based on the name and function of formed proteins and then aligned to the conserved domain database. Furthermore, the functions and characters of formed proteins were described. Based on PCR results, all isolates showed 340 bp DNA band which indicate the presence of ureC gene. The results of BLAST-X, JB2 isolates showed 100% similarity with the α sub-unit ureC gene from Lysinibacillus sphaericus B1-CDA (WP_054549252.1). Whereas, JA1 isolates showed 88% similarity (lowest) with the α sub-unit ureC gene from Bacillus cihuensis FJAT-14515 (WP_028391929.1). The present study reveals that ureC phylogeny can be used in order to investigate ureolytic bacteria species which isolated from calcareous area in East Java province.

scholarly journals RELATION OF ADRENAL CORTICAL HORMONE TO LYMPHOID TISSUE AND LYMPHOCYTES

Blood ◽  
1948 ◽  
Vol 3 (7) ◽  
pp. 729-754 ◽  
Author(s):  
WILLIAM N. VALENTINE ◽  
CHARLES G. CRADDOCK ◽  
JOHN S. LAWRENCE
Keyword(s):  
Adrenal Cortex ◽  
Lymphoid Tissue ◽  
Hormonal Control ◽  
Tissue Structure ◽  
Lymphoid Tissues ◽  
Adrenal Cortical Hormone ◽  
Cortical System ◽  
And Function ◽  
Relationship Of ◽  
The Relationship

Abstract The hormonal control through the hypophyseo-adrenal cortical system of lymphoid tissue structure and function is an important concept. We cannot at the present time regard that the concept is established fact. Final judgment must await additional work and the clarification of some of the inconsistencies which appear to exist. It seems reasonable that lymphoid tissue is one of the end organs of adrenal cortical hormone and that it may perhaps play a role in the response of the organism to stress. It seems quite clear that the sugar hormone of the adrenal cortex is capable of producing structural alterations in lymphoid tissue. Change in thoracic duct lymphocyte numbers as a result of augmentation in the amount of available adrenal cortical hormone is at present controversial. Experiments in this laboratory have failed to demonstrate it. The production of lymphopenia, at least in some species and possibly in man, by increasing available sugar hormone is supported by some evidence. The exact mechanism of production of lymphopenia is open to question, its relationship to changes in lymphoid tissue structure being one of inference. The converse situation—absolute lympocytosis resulting from deprivation of adrenal cortical hormone—is the subject of controversial reports. At best, it must be admitted that relatively slight alterations from the accepted normal range of lymphocyte values occur in the adrenal insufficient organism. Changes in plasma gamma globulins and antibody titers associated with changes in the amount of available cortical hormone are reported. It should be clarified whether such changes have necessarily resulted from lymphocyte dissolution or are related to other of the variegated actions of adrenal cortical hormone. The relationship of adrenal cortical hormone to lymphoid tissue and lymphocytes and the relationship of the latter to the response of the organism to stress must indeed be complex. It is reasonably well established that the life span of the lymphocyte is very short indeed1,58,22 and each lymphocyte presumably liberates its metabolically important contents within a few hours at the most. If stress continues for any period of time, as often it does, it is difficult to visualize the wisdom of interfering with the production of metabolically vital substances in order to secure the transient benefits of lymphoid tissue dissolution. It is also somewhat difficult to regard as proved that the various changes reported after hormone augmentation or deprivation necessarily represent the normal mechanism by which these factors are regulated and kept within physiologic limits. More investigations are required to answer such questions and to further elucidate the interrelationship of the adrenal cortex and lymphoid tissues.

A Research on the Morphology and Composition of Flocs (Part 1: Floc Breaage Disregarded)

2013 ◽  
Vol 726-731 ◽  
pp. 1566-1572 ◽  
Author(s):  
Shi Qiang Ding ◽  
Qing Na Li ◽  
Xin Rong Pang ◽  
Ji Run Xu
Keyword(s):  
Dimensional Space ◽  
Three Dimensional ◽  
New Classification ◽  
Suspension Viscosity ◽  
Primary Particles ◽  
Long Time ◽  
Relationship Of ◽  
The Relationship ◽  
Three Dimensional Space ◽  
Floc Breakage

The characteristics of flocs aggregated in flocculation have been paid more and more attention for a long time. In this paper, a new classification and analyses method dealing with the flocs is developed. The flocs formed after flocculation is divided into four kinds, including the left primary particles, linear flocs with all component particles in a line, planar flocs with all component particles on a plane and volumetric flocs with all component particles in a three-dimensional space. By analyzing the formation approaches of different kind of flocs regardless of the floc breakage, the number of every kind of floc is analyzed to be related with the suspension concentration mathematically. After comparing the different items in the models describing the relationship of floc number and concentration, a series of simplified expressions are presented. Lastly, a mathematical equation relating the measurable suspension viscosity with the numbers of different flocs is obtained.

Block of Human Heart hH1 Sodium Channels by the Enantiomers of Bupivacaine

2000 ◽  
Vol 93 (4) ◽  
pp. 1022-1033 ◽  
Author(s):  
Carla Nau ◽  
Sho-Ya Wang ◽  
Gary R. Strichartz ◽  
Ging Kuo Wang
Keyword(s):  
Human Heart ◽  
Point Mutations ◽  
Cell Voltage ◽  
Site Directed Mutagenesis ◽  
Na Channel ◽  
Amino Acid Residues ◽  
Na Channels ◽  
State Dependent ◽  
Positively Charged

Background S(-)-bupivacaine reportedly exhibits lower cardiotoxicity but similar local anesthetic potency compared with R(+)-bupivacaine. The bupivacaine binding site in human heart (hH1) Na+ channels has not been studied to date. The authors investigated the interaction of bupivacaine enantiomers with hH1 Na+ channels, assessed the contribution of putatively relevant residues to binding, and compared the intrinsic affinities to another isoform, the rat skeletal muscle (mu1) Na+ channel. Methods Human heart and mu1 Na+ channel alpha subunits were transiently expressed in HEK293t cells and investigated during whole cell voltage-clamp conditions. Using site-directed mutagenesis, the authors created point mutations at positions hH1-F1760, hH1-N1765, hH1-Y1767, and hH1-N406 by introducing the positively charged lysine (K) or the negatively charged aspartic acid (D) and studied their influence on state-dependent block by bupivacaine enantiomers. Results Inactivated hH1 Na+ channels displayed a weak stereoselectivity with a stereopotency ratio (+/-) of 1.5. In mutations hH1-F1760K and hH1-N1765K, bupivacaine affinity of inactivated channels was reduced by approximately 20- to 40-fold, in mutation hH1-N406K by approximately sevenfold, and in mutations hH1-Y1767K and hH1-Y1767D by approximately twofold to threefold. Changes in recovery of inactivated mutant channels from block paralleled those of inactivated channel affinity. Inactivated hH1 Na+ channels exhibited a slightly higher intrinsic affinity than mu1 Na+ channels. Conclusions Differences in bupivacaine stereoselectivity and intrinsic affinity between hH1 and mu1 Na+ channels are small and most likely of minor clinical relevance. Amino acid residues in positions hH1-F1760, hH1-N1765, and hH1-N406 may contribute to binding of bupivacaine enantiomers in hH1 Na+ channels, whereas the role of hH1-Y1767 remains unclear.

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