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Article ; Online: Common Mechanism of Activated Catalysis in P-loop Fold Nucleoside Triphosphatases-United in Diversity.

Kozlova, Maria I / Shalaeva, Daria N / Dibrova, Daria V / Mulkidjanian, Armen Y

2022 Volume 12, Issue 10

Abstract: To clarify the obscure hydrolysis mechanism of ubiquitous P-loop-fold nucleoside triphosphatases (Walker NTPases), we analysed the structures of 3136 catalytic sites with bound Mg-NTP complexes or their analogues. Our results are presented in two ... ...

Abstract	To clarify the obscure hydrolysis mechanism of ubiquitous P-loop-fold nucleoside triphosphatases (Walker NTPases), we analysed the structures of 3136 catalytic sites with bound Mg-NTP complexes or their analogues. Our results are presented in two articles; here, in the second of them, we elucidated whether the Walker A and Walker B sequence motifs-common to all P-loop NTPases-could be directly involved in catalysis. We found that the hydrogen bonds (H-bonds) between the strictly conserved, Mg-coordinating Ser/Thr of the Walker A motif ([Ser/Thr]<sup>WA</sup>) and aspartate of the Walker B motif (Asp<sup>WB</sup>) are particularly short (even as short as 2.4 ångströms) in the structures with bound transition state (TS) analogues. Given that a short H-bond implies parity in the pKa values of the H-bond partners, we suggest that, in response to the interactions of a P-loop NTPase with its cognate activating partner, a proton relocates from [Ser/Thr]<sup>WA</sup> to Asp<sup>WB</sup>. The resulting anionic [Ser/Thr]<sup>WA</sup> alkoxide withdraws a proton from the catalytic water molecule, and the nascent hydroxyl attacks the gamma phosphate of NTP. When the gamma-phosphate breaks away, the trapped proton at Asp<sup>WB</sup> passes by the Grotthuss relay via [Ser/Thr]<sup>WA</sup> to beta-phosphate and compensates for its developing negative charge that is thought to be responsible for the activation barrier of hydrolysis.
MeSH term(s)	Nucleoside-Triphosphatase/chemistry ; Nucleoside-Triphosphatase/metabolism ; AAA Domain ; Aspartic Acid ; Protons ; Nucleosides ; Catalysis ; Water/metabolism ; AAA Proteins/metabolism ; Phosphates/metabolism
Chemical Substances	Nucleoside-Triphosphatase (EC 3.6.1.15) ; Aspartic Acid (30KYC7MIAI) ; Protons ; Nucleosides ; Water (059QF0KO0R) ; AAA Proteins (EC 3.6.4.-) ; Phosphates
Language	English
Publishing date	2022-09-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12101346
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Article ; Online: Common Patterns of Hydrolysis Initiation in P-loop Fold Nucleoside Triphosphatases.

Kozlova, Maria I / Shalaeva, Daria N / Dibrova, Daria V / Mulkidjanian, Armen Y

Biomolecules

2022 Volume 12, Issue 10

Abstract: The P-loop fold nucleoside triphosphate (NTP) hydrolases (also known as Walker NTPases) function as ATPases, GTPases, and ATP synthases, are often of medical importance, and represent one of the largest and evolutionarily oldest families of enzymes. ... ...

Abstract	The P-loop fold nucleoside triphosphate (NTP) hydrolases (also known as Walker NTPases) function as ATPases, GTPases, and ATP synthases, are often of medical importance, and represent one of the largest and evolutionarily oldest families of enzymes. There is still no consensus on their catalytic mechanism. To clarify this, we performed the first comparative structural analysis of more than 3100 structures of P-loop NTPases that contain bound substrate Mg-NTPs or their analogues. We proceeded on the assumption that structural features common to these P-loop NTPases may be essential for catalysis. Our results are presented in two articles. Here, in the first, we consider the structural elements that stimulate hydrolysis. Upon interaction of P-loop NTPases with their cognate activating partners (RNA/DNA/protein domains), specific stimulatory moieties, usually Arg or Lys residues, are inserted into the catalytic site and initiate the cleavage of gamma phosphate. By analyzing a plethora of structures, we found that the only shared feature was the mechanistic interaction of stimulators with the oxygen atoms of gamma-phosphate group, capable of causing its rotation. One of the oxygen atoms of gamma phosphate coordinates the cofactor Mg ion. The rotation must pull this oxygen atom away from the Mg ion. This rearrangement should affect the properties of the other Mg ligands and may initiate hydrolysis according to the mechanism elaborated in the second article.
MeSH term(s)	Nucleoside-Triphosphatase/chemistry ; Nucleoside-Triphosphatase/metabolism ; Hydrolysis ; AAA Domain ; Nucleosides ; Adenosine Triphosphatases/metabolism ; GTP Phosphohydrolases/metabolism ; Adenosine Triphosphate/metabolism ; DNA ; RNA ; Phosphates/metabolism ; AAA Proteins/metabolism ; Oxygen/metabolism
Chemical Substances	Nucleoside-Triphosphatase (EC 3.6.1.15) ; Nucleosides ; Adenosine Triphosphatases (EC 3.6.1.-) ; GTP Phosphohydrolases (EC 3.6.1.-) ; Adenosine Triphosphate (8L70Q75FXE) ; DNA (9007-49-2) ; RNA (63231-63-0) ; Phosphates ; AAA Proteins (EC 3.6.4.-) ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-09-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12101345
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Article ; Online: Innate Immunity as an Executor of the Programmed Death of Individual Organisms for the Benefit of the Entire Population.

Chernyak, Boris V / Lyamzaev, Konstantin G / Mulkidjanian, Armen Y

International journal of molecular sciences

2021 Volume 22, Issue 24

Abstract: In humans, over-activation of innate immunity in response to viral or bacterial infections often causes severe illness and death. Furthermore, similar mechanisms related to innate immunity can cause pathogenesis and death in sepsis, massive trauma ( ... ...

Abstract	In humans, over-activation of innate immunity in response to viral or bacterial infections often causes severe illness and death. Furthermore, similar mechanisms related to innate immunity can cause pathogenesis and death in sepsis, massive trauma (including surgery and burns), ischemia/reperfusion, some toxic lesions, and viral infections including COVID-19. Based on the reviewed observations, we suggest that such severe outcomes may be manifestations of a controlled suicidal strategy protecting the entire population from the spread of pathogens and from dangerous pathologies rather than an aberrant hyperstimulation of defense responses. We argue that innate immunity may be involved in the implementation of an altruistic programmed death of an organism aimed at increasing the well-being of the whole community. We discuss possible ways to suppress this atavistic program by interfering with innate immunity and suggest that combating this program should be a major goal of future medicine.
MeSH term(s)	Altruism ; Animals ; Apoptosis/immunology ; COVID-19/immunology ; Cell Death/immunology ; Cytokine Release Syndrome/immunology ; Cytokine Release Syndrome/mortality ; Humans ; Immunity, Innate/immunology ; Inflammasomes/immunology ; Inflammation/immunology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Signal Transduction/immunology
Chemical Substances	Inflammasomes
Language	English
Publishing date	2021-12-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222413480
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Article ; Online: The microtubule skeleton and the evolution of neuronal complexity in vertebrates.

Trushina, Nataliya I / Mulkidjanian, Armen Y / Brandt, Roland

Biological chemistry

2019 Volume 400, Issue 9, Page(s) 1163–1179

Abstract: The evolution of a highly developed nervous system is mirrored by the ability of individual neurons to develop increased morphological complexity. As microtubules (MTs) are crucially involved in neuronal development, we tested the hypothesis that the ... ...

Abstract	The evolution of a highly developed nervous system is mirrored by the ability of individual neurons to develop increased morphological complexity. As microtubules (MTs) are crucially involved in neuronal development, we tested the hypothesis that the evolution of complexity is driven by an increasing capacity of the MT system for regulated molecular interactions as it may be implemented by a higher number of molecular players and a greater ability of the individual molecules to interact. We performed bioinformatics analysis on different classes of components of the vertebrate neuronal MT cytoskeleton. We show that the number of orthologs of tubulin structure proteins, MT-binding proteins and tubulin-sequestering proteins expanded during vertebrate evolution. We observed that protein diversity of MT-binding and tubulin-sequestering proteins increased by alternative splicing. In addition, we found that regions of the MT-binding protein tau and MAP6 displayed a clear increase in disorder extent during evolution. The data provide evidence that vertebrate evolution is paralleled by gene expansions, changes in alternative splicing and evolution of coding sequences of components of the MT system. The results suggest that in particular evolutionary changes in tubulin-structure proteins, MT-binding proteins and tubulin-sequestering proteins were prominent drivers for the development of increased neuronal complexity.
MeSH term(s)	Animals ; Biological Evolution ; Microtubules/metabolism ; Neurons/metabolism ; Vertebrates ; tau Proteins/metabolism
Chemical Substances	tau Proteins
Language	English
Publishing date	2019-05-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1334659-3
ISSN	1437-4315 ; 1431-6730 ; 1432-0355
ISSN (online)	1437-4315
ISSN	1431-6730 ; 1432-0355
DOI	10.1515/hsz-2019-0149
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Article ; Online: Six Functions of Respiration: Isn't It Time to Take Control over ROS Production in Mitochondria, and Aging Along with It?

Skulachev, Vladimir P / Vyssokikh, Mikhail Yu / Chernyak, Boris V / Mulkidjanian, Armen Y / Skulachev, Maxim V / Shilovsky, Gregory A / Lyamzaev, Konstantin G / Borisov, Vitaliy B / Severin, Fedor F / Sadovnichii, Victor A

International journal of molecular sciences

2023 Volume 24, Issue 16

Abstract: Cellular respiration is associated with at least six distinct but intertwined biological functions. (1) biosynthesis of ATP from ADP and inorganic phosphate, (2) consumption of respiratory substrates, (3) support of membrane transport, (4) conversion of ... ...

Abstract	Cellular respiration is associated with at least six distinct but intertwined biological functions. (1) biosynthesis of ATP from ADP and inorganic phosphate, (2) consumption of respiratory substrates, (3) support of membrane transport, (4) conversion of respiratory energy to heat, (5) removal of oxygen to prevent oxidative damage, and (6) generation of reactive oxygen species (ROS) as signaling molecules. Here we focus on function #6, which helps the organism control its mitochondria. The ROS bursts typically occur when the mitochondrial membrane potential (MMP) becomes too high, e.g., due to mitochondrial malfunction, leading to cardiolipin (CL) oxidation. Depending on the intensity of CL damage, specific programs for the elimination of damaged mitochondria (mitophagy), whole cells (apoptosis), or organisms (phenoptosis) can be activated. In particular, we consider those mechanisms that suppress ROS generation by enabling ATP synthesis at low MMP levels. We discuss evidence that the mild depolarization mechanism of direct ATP/ADP exchange across mammalian inner and outer mitochondrial membranes weakens with age. We review recent data showing that by protecting CL from oxidation, mitochondria-targeted antioxidants decrease lethality in response to many potentially deadly shock insults. Thus, targeting ROS- and CL-dependent pathways may prevent acute mortality and, hopefully, slow aging.
MeSH term(s)	Animals ; Reactive Oxygen Species ; Respiration ; Mitochondria ; Aging ; Cardiolipins ; Adenosine Triphosphate ; Mammals
Chemical Substances	Reactive Oxygen Species ; Cardiolipins ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2023-08-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241612540
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Article: Activated Q-cycle as a common mechanism for cytochrome bc1 and cytochrome b6f complexes.

Mulkidjanian, Armen Y

Biochimica et biophysica acta

2010 Volume 1797, Issue 12, Page(s) 1858–1868

Abstract: Cytochrome bc(1)-complexes of animals and bacteria (hereafter bc(1)), as well as related cytochrome b(6)f complexes of plants and cyanobacteria (hereafter bf) are dimeric quinol:cytochrome c/plastocyanin oxidoreductases capable of translocating protons ... ...

Abstract	Cytochrome bc(1)-complexes of animals and bacteria (hereafter bc(1)), as well as related cytochrome b(6)f complexes of plants and cyanobacteria (hereafter bf) are dimeric quinol:cytochrome c/plastocyanin oxidoreductases capable of translocating protons across energy-converting membranes. The commonly accepted Q-cycle mechanism suggests that these enzymes oxidize two quinol molecules in their catalytic centers P to yield one quinol molecule in another catalytic center N. Earlier, based upon data on flash-induced redox changes of cytochromes b and c(1), voltage generation, and proton transfer in membrane vesicles of Rhodobacter capsulatus, we have put forward a scheme of an "activated Q-cycle" for the bc(1). The scheme suggests that the bc(1) dimers, being "activated" by injection of electrons from the membrane ubiquinol pool via centers N, steadily contain two electrons in their cytochrome b moieties under physiological conditions, most likely, as a bound semiquinone in center N of one monomer and a reduced high-potential heme b in the other monomer. Then the oxidation of each ubiquinol molecule in centers P of an activated bc(1) should result in a complete catalytic cycle leading to the formation of a ubiquinole molecule in the one of enzyme's centers N and to voltage generation. Here it is argued that a similar pre-loading by two electrons can explain the available data on flash-induced reactions in cytochrome b(6)f-complexes of green plants and cyanobacteria.
MeSH term(s)	Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Benzoquinones/chemistry ; Benzoquinones/metabolism ; Binding Sites ; Cytochrome b6f Complex/chemistry ; Cytochrome b6f Complex/metabolism ; Electron Transport ; Electron Transport Complex III/chemistry ; Electron Transport Complex III/metabolism ; Models, Chemical ; Oxidation-Reduction ; Plant Proteins/chemistry ; Plant Proteins/metabolism ; Rhodobacter capsulatus/enzymology
Chemical Substances	Bacterial Proteins ; Benzoquinones ; Plant Proteins ; quinone (3T006GV98U) ; Cytochrome b6f Complex (9035-40-9) ; Electron Transport Complex III (EC 1.10.2.2)
Language	English
Publishing date	2010-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbabio.2010.07.008
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Article ; Online: Expansion of the "Sodium World" through Evolutionary Time and Taxonomic Space.

Kozlova, M I / Bushmakin, I M / Belyaeva, J D / Shalaeva, D N / Dibrova, D V / Cherepanov, D A / Mulkidjanian, A Y

Biochemistry. Biokhimiia

2021 Volume 85, Issue 12, Page(s) 1518–1542

Abstract: In 1986, Vladimir Skulachev and his colleagues coined the term "Sodium World" for the group of diverse organisms with sodium (Na)-based bioenergetics. Albeit only few such organisms had been discovered by that time, the authors insightfully noted that " ... ...

Abstract	In 1986, Vladimir Skulachev and his colleagues coined the term "Sodium World" for the group of diverse organisms with sodium (Na)-based bioenergetics. Albeit only few such organisms had been discovered by that time, the authors insightfully noted that "the great taxonomic variety of organisms employing the Na-cycle points to the ubiquitous distribution of this novel type of membrane-linked energy transductions". Here we used tools of bioinformatics to follow expansion of the Sodium World through the evolutionary time and taxonomic space. We searched for those membrane protein families in prokaryotic genomes that correlate with the use of the Na-potential for ATP synthesis by different organisms. In addition to the known Na-translocators, we found a plethora of uncharacterized protein families; most of them show no homology with studied proteins. In addition, we traced the presence of Na-based energetics in many novel archaeal and bacterial clades, which were recently identified by metagenomic techniques. The data obtained support the view that the Na-based energetics preceded the proton-dependent energetics in evolution and prevailed during the first two billion years of the Earth history before the oxygenation of atmosphere. Hence, the full capacity of Na-based energetics in prokaryotes remains largely unexplored. The Sodium World expanded owing to the acquisition of new functions by Na-translocating systems. Specifically, most classes of G-protein-coupled receptors (GPCRs), which are targeted by almost half of the known drugs, appear to evolve from the Na-translocating microbial rhodopsins. Thereby the GPCRs of class A, with 700 representatives in human genome, retained the Na-binding site in the center of the transmembrane heptahelical bundle together with the capacity of Na-translocation. Mathematical modeling showed that the class A GPCRs could use the energy of transmembrane Na-potential for increasing both their sensitivity and selectivity. Thus, GPCRs, the largest protein family coded by human genome, stem from the Sodium World, which encourages exploration of other Na-dependent enzymes of eukaryotes.
MeSH term(s)	Archaea/genetics ; Archaea/metabolism ; Bacteria/genetics ; Bacteria/metabolism ; Energy Metabolism/genetics ; Eukaryota/genetics ; Eukaryota/metabolism ; Evolution, Molecular ; Genomics ; Models, Genetic ; Receptors, G-Protein-Coupled ; Sodium/metabolism
Chemical Substances	Receptors, G-Protein-Coupled ; Sodium (9NEZ333N27)
Language	English
Publishing date	2021-03-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297920120056
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Article ; Online: Does Oxidation of Mitochondrial Cardiolipin Trigger a Chain of Antiapoptotic Reactions?

Mulkidjanian, A Y / Shalaeva, D N / Lyamzaev, K G / Chernyak, B V

Biochemistry. Biokhimiia

2018 Volume 83, Issue 10, Page(s) 1263–1278

Abstract: Oxidative stress causes selective oxidation of cardiolipin (CL), a four-tail lipid specific for the inner mitochondrial membrane. Interaction with oxidized CL transforms cytochrome c into peroxidase capable of oxidizing even more CL molecules. Ultimately, ...

Abstract	Oxidative stress causes selective oxidation of cardiolipin (CL), a four-tail lipid specific for the inner mitochondrial membrane. Interaction with oxidized CL transforms cytochrome c into peroxidase capable of oxidizing even more CL molecules. Ultimately, this chain of events leads to the pore formation in the outer mitochondrial membrane and release of mitochondrial proteins, including cytochrome c, into the cytoplasm. In the cytoplasm, cytochrome c promotes apoptosome assembly that triggers apoptosis (programmed cell death). Because of this amplification cascade, even an occasional oxidation of a single CL molecule by endogenously formed reactive oxygen species (ROS) might cause cell death, unless the same CL oxidation triggers a separate chain of antiapoptotic reactions that would prevent the CL-mediated apoptotic cascade. Here, we argue that the key function of CL in mitochondria and other coupling membranes is to prevent proton leak along the interface of interacting membrane proteins. Therefore, CL oxidation should increase proton permeability through the CL-rich clusters of membrane proteins (CL islands) and cause a drop in the mitochondrial membrane potential (MMP). On one hand, the MMP drop should hinder ROS generation and further CL oxidation in the entire mitochondrion. On the other hand, it is known to cause rapid fission of the mitochondrial network and formation of many small mitochondria, only some of which would contain oxidized CL islands. The fission of mitochondrial network would hinder apoptosome formation by preventing cytochrome c release from healthy mitochondria, so that slowly working protein quality control mechanisms would have enough time to eliminate mitochondria with the oxidized CL. Because of these two oppositely directed regulatory pathways, both triggered by CL oxidation, the fate of the cell appears to be determined by the balance between the CL-mediated proapoptotic and antiapoptotic reactions. Since this balance depends on the extent of CL oxidation, mitochondria-targeted antioxidants might be able to ensure cell survival in many pathologies by preventing CL oxidation.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antioxidants/chemistry ; Apoptosis ; Cardiolipins/chemistry ; Cardiolipins/metabolism ; Cytochromes c/metabolism ; Humans ; Membrane Potential, Mitochondrial ; Mice ; Mitochondria/metabolism ; Mitochondrial Degradation ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Sequence Alignment ; Uncoupling Protein 1/chemistry ; Uncoupling Protein 1/metabolism
Chemical Substances	Antioxidants ; Cardiolipins ; Reactive Oxygen Species ; Ucp1 protein, mouse ; Uncoupling Protein 1 ; Cytochromes c (9007-43-6)
Language	English
Publishing date	2018-11-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297918100115
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Article ; Online: G protein-coupled receptors of class A harness the energy of membrane potential to increase their sensitivity and selectivity.

Shalaeva, Daria N / Cherepanov, Dmitry A / Galperin, Michael Y / Vriend, Gert / Mulkidjanian, Armen Y

Biochimica et biophysica acta. Biomembranes

2019 Volume 1861, Issue 12, Page(s) 183051

Abstract: The human genome contains about 700 genes of G protein-coupled receptors (GPCRs) of class A; these seven-helical membrane proteins are the targets of almost half of all known drugs. In the middle of the helix bundle, crystal structures reveal a highly ... ...

Abstract	The human genome contains about 700 genes of G protein-coupled receptors (GPCRs) of class A; these seven-helical membrane proteins are the targets of almost half of all known drugs. In the middle of the helix bundle, crystal structures reveal a highly conserved sodium-binding site, which is connected with the extracellular side by a water-filled tunnel. This binding site contains a sodium ion in those GPCRs that are crystallized in their inactive conformations but does not in those GPCRs that are trapped in agonist-bound active conformations. The escape route of the sodium ion upon the inactive-to-active transition and its very direction have until now remained obscure. Here, by modeling the available experimental data, we show that the sodium gradient over the cell membrane increases the sensitivity of GPCRs if their activation is thermodynamically coupled to the sodium ion translocation into the cytoplasm but decreases it if the sodium ion retreats into the extracellular space upon receptor activation. The model quantitatively describes the available data on both activation and suppression of distinct GPCRs by membrane voltage. The model also predicts selective amplification of the signal from (endogenous) agonists if only they, but not their (partial) analogs, induce sodium translocation. Comparative structure and sequence analyses of sodium-binding GPCRs indicate a key role for the conserved leucine residue in the second transmembrane helix (Leu2.46) in coupling sodium translocation to receptor activation. Hence, class A GPCRs appear to harness the energy of the transmembrane sodium potential to increase their sensitivity and selectivity.
MeSH term(s)	Binding Sites/physiology ; Biological Transport, Active/physiology ; Cell Membrane/metabolism ; Humans ; Membrane Potentials/physiology ; Models, Molecular ; Models, Theoretical ; Protein Binding/physiology ; Receptors, G-Protein-Coupled/metabolism ; Receptors, G-Protein-Coupled/physiology ; Sodium/metabolism
Chemical Substances	Receptors, G-Protein-Coupled ; Sodium (9NEZ333N27)
Language	English
Publishing date	2019-08-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamem.2019.183051
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Article ; Online: Phylogenomic Analysis Identifies a Sodium-Translocating Decarboxylating Oxidoreductase in Thermotogae.

Klimchuk, O I / Dibrova, D V / Mulkidjanian, A Y

Biochemistry. Biokhimiia

2016 Volume 81, Issue 5, Page(s) 481–490

Abstract: Bacterial sodium-dependent decarboxylases were the first enzymes exemplifying sodium-dependent bioenergetics. These enzyme complexes couple decarboxylation of organic acids with the export of sodium ions via a special membrane subunit. In 711 ... ...

Abstract	Bacterial sodium-dependent decarboxylases were the first enzymes exemplifying sodium-dependent bioenergetics. These enzyme complexes couple decarboxylation of organic acids with the export of sodium ions via a special membrane subunit. In 711 representative prokaryotic genomes, we have analyzed genomic neighborhoods of the genes that code the membrane subunit of sodium decarboxylases. In representatives of Thermotogae, the operons with the gene of this subunit lack the genes of subunits that perform non-oxidative decarboxylation. Instead, these operons contain the genes of alpha- and delta-subunits of decarboxylating oxidoreductases of alpha-ketoacids. The genes of beta- and gamma-subunits of the decarboxylating oxidoreductases were found within the genomes of respective Thermotogae species as separate, two-gene operons. We suggest that the described two operons code together for sodium-translocating decarboxylating oxidoreductases capable of coupling oxidative decarboxylation of alpha-ketoacids with the export of sodium ions, which is a novel type of bioenergetic coupling.
MeSH term(s)	Amino Acid Sequence ; Bacteria/enzymology ; Bacterial Proteins/chemistry ; Bacterial Proteins/classification ; Decarboxylation ; Molecular Sequence Data ; Oxidoreductases/chemistry ; Oxidoreductases/classification ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment
Chemical Substances	Bacterial Proteins ; Oxidoreductases (EC 1.-)
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1109-5
ISSN	1608-3040 ; 0006-2979 ; 0320-9717
ISSN (online)	1608-3040
ISSN	0006-2979 ; 0320-9717
DOI	10.1134/S0006297916050059
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