scholarly journals Proton-assisted Two-electron Transfer in Natural Variants of Tetraheme Cytochromes fromDesulfomicrobiumSp.

2004 ◽  
Vol 279 (50) ◽  
pp. 52227-52237 ◽  
Author(s):  
Ilídio J. Correia ◽  
Catarina M. Paquete ◽  
Ana Coelho ◽  
Claudia C. Almeida ◽  
Teresa Catarino ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Amino Acid ◽  
Hydrogen Uptake ◽  
Single Amino Acid ◽  
Amino Acid Residues ◽  
Tertiary Structures ◽  
X Ray Crystallography ◽  
Natural Variants ◽  
Uptake Activity ◽  
Tetraheme Cytochrome

The tetraheme cytochromec3isolated fromDesulfomicrobium baculatum(DSM 1743)(Dsmb) was cloned, and the sequence analysis showed that this cytochrome differs in just three amino acid residues from the cytochromec3isolated fromDesulfomicrobium norvegicum(Dsmn): (DsmnXXDsmb) Thr-37 → Ser, Val-45 → Ala, and Phe-88 → Tyr. X-ray crystallography was used to determine the structure of cytochromec3fromDsmb, showing that it is very similar to the published structure of cytochromec3fromDsmn. A detailed thermodynamic and kinetic characterization of these two tetraheme cytochromesc3was performed by using NMR and visible spectroscopy. The results obtained show that the network of cooperativities between the redox and protonic centers is consistent with a synergetic process to stimulate the hydrogen uptake activity of hydrogenase. This is achieved by increasing the affinity of the cytochrome for protons through binding electrons and, reciprocally, by favoring a concerted two-electron transfer assisted by the binding of proton(s). The data were analyzed within the framework of the differences in the primary and tertiary structures of the two proteins, showing that residue 88, close to heme I, is the main cause for the differences in the microscopic thermodynamic parameters obtained for these two cytochromesc3. This comparison reveals how replacement of a single amino acid can tune the functional properties of energy-transducing proteins, so that they can be optimized to suit the bioenergetic constraints of specific habitats.

scholarly journals Natural variants in SARS-CoV-2 Spike protein pinpoint structural and functional hotspots with implications for prophylaxis and therapeutic strategies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suman Pokhrel ◽  
Benjamin R. Kraemer ◽  
Scott Burkholz ◽  
Daria Mochly-Rosen
Keyword(s):  
Amino Acid ◽  
Severe Disease ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Severe Respiratory Distress ◽  
S Protein ◽  
Individual Sequences ◽  
Natural Variants ◽  
Novel Coronavirus ◽  
The Individual

AbstractIn December 2019, a novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of pneumonia with severe respiratory distress and outbreaks in Wuhan, China. The rapid and global spread of SARS-CoV-2 resulted in the coronavirus 2019 (COVID-19) pandemic. Earlier during the pandemic, there were limited genetic viral variations. As millions of people became infected, multiple single amino acid substitutions emerged. Many of these substitutions have no consequences. However, some of the new variants show a greater infection rate, more severe disease, and reduced sensitivity to current prophylaxes and treatments. Of particular importance in SARS-CoV-2 transmission are mutations that occur in the Spike (S) protein, the protein on the viral outer envelope that binds to the human angiotensin-converting enzyme receptor (hACE2). Here, we conducted a comprehensive analysis of 441,168 individual virus sequences isolated from humans throughout the world. From the individual sequences, we identified 3540 unique amino acid substitutions in the S protein. Analysis of these different variants in the S protein pinpointed important functional and structural sites in the protein. This information may guide the development of effective vaccines and therapeutics to help arrest the spread of the COVID-19 pandemic.

scholarly journals Identification of critical amino acid residues in the regulatory N-terminal domain of PMEL

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Susan M. Mitchell ◽  
Morven Graham ◽  
Xinran Liu ◽  
Ralf M. Leonhardt
Keyword(s):  
Amino Acid ◽  
Pigment Cell ◽  
Specific Protein ◽  
Single Amino Acid ◽  
Amyloid Formation ◽  
Amino Acid Residues ◽  
Proteolytic Fragment ◽  
The Core ◽  
N Terminus ◽  
In Cis

AbstractThe pigment cell-specific protein PMEL forms a functional amyloid matrix in melanosomes onto which the pigment melanin is deposited. The amyloid core consists of a short proteolytic fragment, which we have termed the core-amyloid fragment (CAF) and perhaps additional parts of the protein, such as the PKD domain. A highly O-glycosylated repeat (RPT) domain also derived from PMEL proteolysis associates with the amyloid and is necessary to establish the sheet-like morphology of the assemblies. Excluded from the aggregate is the regulatory N-terminus, which nevertheless must be linked in cis to the CAF in order to drive amyloid formation. The domain is then likely cleaved away immediately before, during, or immediately after the incorporation of a new CAF subunit into the nascent amyloid. We had previously identified a 21 amino acid long region, which mediates the regulatory activity of the N-terminus towards the CAF. However, many mutations in the respective segment caused misfolding and/or blocked PMEL export from the endoplasmic reticulum, leaving their phenotype hard to interpret. Here, we employ a saturating mutagenesis approach targeting the motif at single amino acid resolution. Our results confirm the critical nature of the PMEL N-terminal region and identify several residues essential for PMEL amyloidogenesis.

A Mutation in the  Subunit of the Platelet Integrin IIbβ3 Identifies a Novel Region Important for Ligand Binding

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 918-924 ◽  
Author(s):  
Eileen Collins Tozer ◽  
Elizabeth K. Baker ◽  
Mark H. Ginsberg ◽  
Joseph C. Loftus
Keyword(s):  
Amino Acid ◽  
Ligand Binding ◽  
Single Amino Acid ◽  
Chimeric Receptor ◽  
Amino Acid Residues ◽  
Genetic Approach ◽  
Specific Amino Acid ◽  
Transfected Cells ◽  
Binding Function ◽  
A Cell

Abstract An unbiased genetic approach was used to identify a specific amino acid residue in the IIb subunit important for the ligand binding function of the integrin IIbβ. Chemically mutagenized cells were selected by flow cytometry based on their inability to bind the ligand mimetic antibody PAC1 and a cell line containing a single amino acid substitution in IIb at position 224 (D→V) was identified. Although well expressed on the surface of transfected cells, IIbD224Vβ3 as well as IIbD224Aβ3 did not bind IIbβ3-specific ligands or a RGD peptide, a ligand shared in common with vβ3. Insertion of exon 5 of IIb, residues G193-W235, into the backbone of the v subunit did not enable the chimeric receptor to bind IIbβ3-specific ligands. However, the chimeric receptor was still capable of binding to a RGD affinity matrix. IIbD224 is not well conserved among other integrin  subunits and is located in a region of significant variability. In addition, amino acid D224 lies within a predicted loop of the recently proposed β-propeller model for integrin  subunits and is adjacent to a loop containing amino acid residues previously implicated in receptor function. These data support a role for this region in ligand binding function of the IIbβ3 receptor.

scholarly journals Amino Acid Residues in the Carboxy-Terminal Region of Cottontail Rabbit Papillomavirus E6 Influence Spontaneous Regression of Cutaneous Papillomas

2002 ◽  
Vol 76 (23) ◽  
pp. 11801-11808 ◽  
Author(s):  
Jiafen Hu ◽  
Nancy M. Cladel ◽  
Martin D. Pickel ◽  
Neil D. Christensen
Keyword(s):  
Amino Acid ◽  
Immune Responses ◽  
Single Amino Acid ◽  
Human Populations ◽  
Amino Acid Residues ◽  
High Frequencies ◽  
Host Immune Responses ◽  
Cottontail Rabbit ◽  
Single Amino Acid Change ◽  
Carboxy Terminal

ABSTRACT Previous studies have identified two different strains of cottontail rabbit papillomavirus (CRPV) that differ by approximately 5% in base pair sequence and that perform quite differently when used to challenge New Zealand White (NZW) rabbit skin. One strain caused persistent lesions (progressor strain), and the other induced papillomas that spontaneously regressed (regressor strain) at high frequencies (J. Salmon, M. Nonnenmacher, S. Caze, P. Flamant, O. Croissant, G. Orth, and F. Breitburd, J. Virol. 74:10766-10777, 2000; J. Salmon, N. Ramoz, P. Cassonnet, G. Orth, and F. Breitburd, Virology 235:228-234, 1997). We generated a panel of CRPV genomes that contained chimeric and mutant progressor and regressor strain E6 genes and assessed the outcome upon infection of both outbred and EIII/JC inbred NZW rabbits. The carboxy-terminal 77-amino-acid region of the regressor CRPV strain E6, which contained 15 amino acid residues that are different from those of the equivalent region of the persistent CRPV strain E6, played a dominant role in the conversion of the persistent CRPV strain to one showing high rates of spontaneous regressions. In addition, a single amino acid change (G252E) in the E6 protein of the CRPV progressor strain led to high frequencies of spontaneous regressions in inbred rabbits. These observations imply that small changes in the amino acid sequences of papillomavirus proteins can dramatically impact the outcome of natural host immune responses to these viral infections. The data imply that intrastrain differences between separate isolates of a single papillomavirus type (such as human papillomavirus type 16) may contribute to a collective variability in host immune responses in outbred human populations.

scholarly journals Identification and Functions of Amino Acid Residues in PotB and PotC Involved in Spermidine Uptake Activity

2010 ◽  
Vol 285 (50) ◽  
pp. 39061-39069 ◽  
Author(s):  
Kyohei Higashi ◽  
Yoshiharu Sakamaki ◽  
Emiko Herai ◽  
Risa Demizu ◽  
Takeshi Uemura ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Residues ◽  
Uptake Activity

Electron Transfer Reaction of Glucose Oxidase Hybrids Modified with PhenothiazineviaPoly(ethylene oxide) Spacer on Acidic Amino Acid Residues

2002 ◽  
Vol 31 (2) ◽  
pp. 256-257 ◽  
Author(s):  
Sayuri Aoki ◽  
Kunikazu Ishii ◽  
Takeshi Ueki ◽  
Kazumichi Ban ◽  
Shin-ichiro Imabayashi ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Amino Acid ◽  
Ethylene Oxide ◽  
Glucose Oxidase ◽  
Transfer Reaction ◽  
Electron Transfer Reaction ◽  
Amino Acid Residues ◽  
Acidic Amino Acid

scholarly journals Molecular Insights Into the Gating Kinetics of the Cardiac hERG Channel, Illuminated by Structure and Molecular Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Zheng Zequn ◽  
Lian Jiangfang
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Molecular Dynamics Simulation ◽  
Dynamics Simulation ◽  
Herg Channel ◽  
Single Amino Acid ◽  
Delayed Rectifier ◽  
Amino Acid Residues ◽  
Structural Domains ◽  
Gating Kinetics

The rapidly activating delayed rectifier K+ current generated by the cardiac hERG potassium channel encoded by KCNH2 is the most important reserve current for cardiac repolarization. The unique inward rectification characteristics of the hERG channel depend on the gating regulation, which involves crucial structural domains and key single amino acid residues in the full-length hERG channel. Identifying critical molecules involved in the regulation of gating kinetics for the hERG channel requires high-resolution structures and molecular dynamics simulation models. Based on the latest progress in hERG structure and molecular dynamics simulation research, summarizing the molecules involved in the changes in the channel state helps to elucidate the unique gating characteristics of the channel and the reason for its high affinity to cardiotoxic drugs. In this review, we aim to summarize the significant advances in understanding the voltage gating regulation of the hERG channel based on its structure obtained from cryo-electron microscopy and computer simulations, which reveal the critical roles of several specific structural domains and amino acid residues.

Sign in / Sign up

Export Citation Format

Share Document