scholarly journals Pro219 is an electrostatic color determinant in the light-driven sodium pump KR2

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuta Nakajima ◽  
Laura Pedraza-González ◽  
Leonardo Barneschi ◽  
Keiichi Inoue ◽  
Massimo Olivucci ◽  
...  
Keyword(s):  
Amino Acid ◽  
Electrostatic Interactions ◽  
Switching Function ◽  
Minor Role ◽  
Amino Acid Residues ◽  
Sodium Pumps ◽  
Environmental Consequences ◽  
Hydrogen Bond Networks ◽  
Microbial Rhodopsin ◽  
A Minor

AbstractColor tuning in animal and microbial rhodopsins has attracted the interest of many researchers, as the color of their common retinal chromophores is modulated by the amino acid residues forming the chromophore cavity. Critical cavity amino acid residues are often called “color switches”, as the rhodopsin color is effectively tuned through their substitution. Well-known color switches are the L/Q and A/TS switches located in the C and G helices of the microbial rhodopsin structure respectively. Recently, we reported on a third G/P switch located in the F helix of the light-driven sodium pumps of KR2 and JsNaR causing substantial spectral red-shifts in the latter with respect to the former. In order to investigate the molecular-level mechanism driving such switching function, here we present an exhaustive mutation, spectroscopic and computational investigation of the P219X mutant set of KR2. To do so, we study the changes in the absorption band of the 19 possible mutants and construct, semi-automatically, the corresponding hybrid quantum mechanics/molecular mechanics models. We found that the P219X feature a red-shifted light absorption with the only exception of P219R. The analysis of the corresponding models indicate that the G/P switch induces red-shifting variations via electrostatic interactions, while replacement-induced chromophore geometrical (steric) distortions play a minor role. However, the same analysis indicates that the P219R blue-shifted variant has a more complex origin involving both electrostatic and steric changes accompanied by protonation state and hydrogen bond networks modifications. These results make it difficult to extract simple rules or formulate theories for predicting how a switch operates without considering the atomistic details and environmental consequences of the side chain replacement.

scholarly journals SLC6A14, a Pivotal Actor on Cancer Stage: When Function Meets Structure

2019 ◽  
Vol 24 (9) ◽  
pp. 928-938 ◽  
Author(s):  
Luca Palazzolo ◽  
Chiara Paravicini ◽  
Tommaso Laurenzi ◽  
Sara Adobati ◽  
Simona Saporiti ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Amino Acid Residues ◽  
Dibasic Amino Acid ◽  
Novel Target ◽  
Function Relationship ◽  
Dynamics Simulations

SLC6A14 (ATB0,+) is a sodium- and chloride-dependent neutral and dibasic amino acid transporter that regulates the distribution of amino acids across cell membranes. The transporter is overexpressed in many human cancers characterized by an increased demand for amino acids; as such, it was recently acknowledged as a novel target for cancer therapy. The knowledge on the molecular mechanism of SLC6A14 transport is still limited, but some elegant studies on related transporters report the involvement of the 12 transmembrane α-helices in the transport mechanism, and describe structural rearrangements mediated by electrostatic interactions with some pivotal gating residues. In the present work, we constructed a SLC6A14 model in outward-facing conformation via homology modeling and used molecular dynamics simulations to predict amino acid residues critical for substrate recognition and translocation. We docked the proteinogenic amino acids and other known substrates in the SLC6A14 binding site to study both gating regions and the exposed residues involved in transport. Interestingly, some of these residues correspond to those previously identified in other LeuT-fold transporters; however, we could also identify a novel relevant residue with such function. For the first time, by combined approaches of molecular docking and molecular dynamics simulations, we highlight the potential role of these residues in neutral amino acid transport. This novel information unravels new aspects of the human SLC6A14 structure–function relationship and may have important outcomes for cancer treatment through the design of novel inhibitors of SLC6A14-mediated transport.

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 The fate of absorbed and exogenous ammonia as influenced by forage or forage–concentrate diets in growing sheep

1996 ◽  
Vol 76 (2) ◽  
pp. 231-248 ◽  
Author(s):  
G. E. Lobley ◽  
P. J. M. Weijs ◽  
A. Connell ◽  
A. G. Calder ◽  
D. S. Brown ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ammonium Salt ◽  
Free Amino ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Minor Role ◽  
N Removal ◽  
A Minor ◽  
Branched Chains

Changes in splanchnic energy and N metabolism were studied in sheep, prepared with vascular catheters across the portal-drained viscera (PDV) and the Liver, and maintained on supramaintenance intakes of either grass or grass + barley pellets. The animals were challenged, on both diets, with 4 d intra- mesenteric vein infusions of NH4CI (25 µmol/min) plus NH4HCO3(at either 0 or 125 µmol/min). On the final day of each treatment the natural abundance NH4Cl was replaced with15NH4Cl over a 10 h infusion while over the same period [l-13C]leucine was infused via a jugular vein. Measurements were made of blood flow plus mass transfers of NH3, urea, free amino acids and O2, across the PDV and liver. Enrichments of [14N15N]urea and [15N15N]urea plus [15N]glutamine, aspartate and glutamate were also monitored. Whole-body urea flux was determined by infusion of [14C]urea. At the end of the study the animals were infused for 3 h with15NH4CI, killed and liver samples assayed for intracellular free amino acid enrichments and concentrations. Blood flows across the splanchnic region were unaffected by either diet or level of ammonium salt infusion. At the lower ammonium salt infusion there was a trend for greater absorption of NH3across the PDV (P<0·10) with grass + barley than with the grass diet, while removal of urea was unaltered. At the higher ammonium salt infusions there was a significantly greater appearance of NH, across the PDV and this exceeded the extra infused. Urea-N removal, however, was also elevated and by more than that required to account for the additional NH3. The PDV contributed 19–28% to whole-body O2consumption and the liver 23–32%. Hepatic extraction of absorbed NH3was complete on all treatments and systemic pH remained constant. The fractions of urea-N apparently derived from NH3, were similar on the grass (0·59–0·64) and grass + barley (0·64–0·67) diets. Hepatic production of urea agreed well with urea flux measurements. Between the two levels of ammonium salt infusion and within diets the additional NH3removed across the PDV was accounted for by the increased urea-N production. The [14N15N]: [15N15N] ratio of the urea produced was 97:3, while the enrichment of hepatic intracellular free aspartate was lower than that of [14N15N]urea. Glutamine enrichments were 0·23–0·37 those of [14N15N]urea, indicating a minor role for those hepatocytes (probably perivenous) which contain glutamine synthetase (EC6.3.1.2). Leucine kinetics, either for the whole body or splanchnic tissues, were not different between diets or level of ammonium salt infusion, except for oxidation which was less on the grassfbarley ration. Amino acid concentrations were lower on the grass + barley diet but net PDV absorptions were similar. The pattern of essential amino acids absorbed into the PDV showed good agreement with the published composition of mixed rumen microbial protein. Fractional disappearances of absorbed free essential amino acids across the liver varied from 0·4 (branched chains) to near unity (histidine, phenylalanine)

scholarly journals The isolation, properties and amino acid sequence of erabutoxin c, a minor neurotoxic component of the venom of a sea snake Laticauda semifasciata

1972 ◽  
Vol 130 (2) ◽  
pp. 547-555 ◽  
Author(s):  
N. Tamiya ◽  
H. Abe
Keyword(s):  
Amino Acid ◽  
Aspartic Acid ◽  
Gel Filtration ◽  
Disc Electrophoresis ◽  
Amino Acid Residues ◽  
Sea Snake ◽  
Acetylcholine Contracture ◽  
Laticauda Semifasciata ◽  
A Minor ◽  
Erabutoxin B

Erabutoxin c, a minor neurotoxic component of the venom of a sea snake Laticauda semifasciata, was isolated in pure form by repeated column chromatography on CM-cellulose columns. The toxin was crystallizable and monodisperse in rechromatography, disc electrophoresis and isoelectric focusing (isoelectric point, pH9.23–9.25). The molecular weight of the toxin, as estimated by gel filtration, was 7000. The toxin showed the same lethal activity to mice (0.13μg/g body wt., intramuscular injection) and the same effect on isolated frog muscle as erabutoxins a and b, the main toxic components of the venom. The toxin inhibited the acetylcholine contracture but not the potassium chloride contracture of muscle. Erabutoxin c consisted of 62 amino acid residues, containing one fewer lysine and one more histidine than erabutoxin a and one fewer lysine and one more aspartic acid (or asparagine) than erabutoxin b. Erabutoxin c was reduced, S-carboxymethylated and hydrolysed with trypsin. The only fragment different from the corresponding fragments from erabutoxin b was hydrolysed further with pepsin. One of the peptic fragments, which was assumed to have the aspartic acid (or asparagine) residue in question at the C-terminal end, was treated with carboxypeptidase A. The C-terminal residue was found to be an asparagine. It was therefore concluded that erabutoxin c was [51-asparagine]-erabutoxin b.

scholarly journals Specific electrostatic interactions between charged amino acid residues regulate binding of von Willebrand factor to blood platelets

2017 ◽  
Vol 292 (45) ◽  
pp. 18608-18617 ◽  
Author(s):  
Gianluca Interlandi ◽  
Olga Yakovenko ◽  
An-Yue Tu ◽  
Jeff Harris ◽  
Jennie Le ◽  
...  
Keyword(s):  
Amino Acid ◽  
Von Willebrand Factor ◽  
Electrostatic Interactions ◽  
Blood Platelets ◽  
Amino Acid Residues ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals On the causes of evolutionary transition:transversion bias

2015 ◽  
Author(s):  
Arlin Stoltzfus ◽  
Ryan W. Norris
Keyword(s):  
Amino Acid ◽  
Statistical Power ◽  
Direct Evidence ◽  
Minor Role ◽  
Single Nucleotide ◽  
Fitness Effects ◽  
A Minor ◽  
Amino Acid Exchangeability ◽  
Growth Experiments ◽  
Null Expectation

A pattern in which nucleotide transitions are favored several-fold over transversions is common in molecular evolution. When this pattern occurs among amino acid replacements, explanations often invoke an effect of selection, on the grounds that transitions are more conservative in their effects on proteins. However, the underlying hypothesis of conservative transitions has never been tested directly. Here we assess support for this hypothesis using direct evidence: the fitness effects of mutations in actual proteins, measured via individual or paired growth experiments. We assembled data from 8 published studies, ranging in size from 24 to 757 single-nucleotide mutations that change an amino acid. Every study has the statistical power to reveal significant effects of amino acid exchangeability, and most studies have the power to discern a binary conservative-vs-radical distinction. However, only one study suggests that transitions are significantly more conservative than transversions. In the combined set of 1239 replacements, the chance that a transition is more conservative than a transversion is 53 % (95 % confidence interval, 50 % to 56 %), compared to the null expectation of 50 %. We show that this effect is not large compared to that of most biochemical factors, and is not large enough to explain the several-fold bias observed in evolution. In short, available data have the power to verify the "conservative transitions" hypothesis if true, but suggest instead that selection on proteins plays at best a minor role in the observed bias.

The role of hydrophobic, aromatic and electrostatic interactions between amino acid residues and a titanium dioxide surface

2018 ◽  
Vol 20 (47) ◽  
pp. 29811-29816 ◽  
Author(s):  
Avia Leader ◽  
Daniel Mandler ◽  
Meital Reches
Keyword(s):  
Amino Acids ◽  
Titanium Dioxide ◽  
Amino Acid ◽  
Electrostatic Interactions ◽  
Amino Acid Residues ◽  
New Materials ◽  
Titanium Dioxide Surface

Understanding the nature of interactions between inorganic surfaces and biomolecules, such as amino acids and peptides, can enhance the development of new materials.

scholarly journals Electrostatic interactions play a minor role in the binding of ExoS to 14-3-3 proteins

2010 ◽  
Vol 427 (2) ◽  
pp. 217-224 ◽  
Author(s):  
Lubna Yasmin ◽  
Jeffrey L. Veesenmeyer ◽  
Maureen H. Diaz ◽  
Matthew S. Francis ◽  
Christian Ottmann ◽  
...  
Keyword(s):  
Cell Death ◽  
Electrostatic Interaction ◽  
Interaction Potential ◽  
Stress Responses ◽  
Electrostatic Interactions ◽  
Cell Metabolism ◽  
Structural Basis ◽  
Minor Role ◽  
Secondary Importance ◽  
A Minor

14-3-3 proteins belong to a family of conserved molecules expressed in all eukaryotic cells that play an important role in a multitude of signalling pathways. 14-3-3 proteins bind either to phosphoserine/phosphothreonine residues or to sequence-specific non-phosphorylated motifs in more than 200 interaction partners [Pozuelo Rubio, Geraghty, Wong, Wood, Campbell, Morrice and Mackintosh (2004) Biochem. J. 379, 395–408]. These interactions result in cell-cycle regulation, apoptosis, stress responses, cell metabolism and malignant transformation. One example of a phosphorylation-independent interaction is the binding of 14-3-3 to ExoS (exoenzyme S), a bacterial ADP-ribosyltransferase toxin of Pseudomonas aeruginosa. In the present study, we have utilized additional biochemical and infection analyses to define further the structural basis of the interaction between ExoS and 14-3-3. An ExoS leucine-substitution mutant dramatically reduced the interaction potential with 14-3-3 suggesting that Leu422, Leu423, Leu426 and Leu428 of ExoS are important for its interaction with 14-3-3, its enzymatic activity and cytotoxicity. However, ExoS substitution mutants of residues that interact with 14-3-3 through an electrostatic interaction, such as Ser416, His418, Asp424 and Asp427, showed no reduction in their interaction potential with 14-3-3. These ExoS substitution mutants were also as aggressive as wild-type ExoS at inducing cell death and to modify endogenous ExoS target within the cell. In conclusion, electrostatic interaction between ExoS and 14-3-3 via polar residues (Ser416, His418, Asp424 and Asp427) appears to be of secondary importance. Thus the interaction between the ‘roof’ of the groove of 14-3-3 and ExoS relies more on hydrophobic interaction forces, which probably contributes to induce cell death after ExoS infection and activation.

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