scholarly journals How does the mood stabilizer lithium bind ATP, the energy currency of the cell

2019 ◽  
Author(s):  
A. Haimovich ◽  
A. Goldbourt
Keyword(s):  
Small Molecules ◽  
Solid State Nmr ◽  
Molecular Basis ◽  
Mood Stabilizer ◽  
Sodium Ions ◽  
Lithium Ions ◽  
Cellular Targets ◽  
Biochemical Pathways ◽  
Narrow Therapeutic Range ◽  
Fourth Coordination

AbstractLithium, in the form of a salt, is a mood stabilizer and a leading drug for the treatment of bipolar disorder. It has a very narrow therapeutic range and a variety of side effects. Lithium can replace magnesium and other cations in enzymes and small molecules, among them ATP, thereby affecting and inhibiting many biochemical pathways. The form of binding of lithium ions to ATP is not known.Here we extract the binding environment of lithium in solid ATP using a multi-nuclear multi-dimensional solid-state NMR approach.We determine that the coordination sphere of lithium includes, at a distance of 3.0(±0.4) Å, three phosphates; the two phosphates closest to the ribose ring from one ATP molecule, and the middle phosphate from another ATP molecule. A water molecule most probably completes the fourth coordination. Despite the use of excess lithium in the preparations, sodium ions still remain bound to the sample, at distances of 4.3-5.5 Å from Li, and coordinate the first phosphate and two terminal phosphates.In conclusion, solid-state NMR enables to unravel the exact coordination of lithium in ATP showing binding to three phosphates from two molecules, none of which are the terminal gamma phosphate. The methods we use are applicable to study lithium bound to a variety of ATP-bound enzymes, or to other cellular targets of lithium, consequently suggesting a molecular basis for its mode of action.

Adsorption of Small Molecules on Cu3(btc)2 and Cu3–xZnx(btc)2 Metal–Organic Frameworks (MOF) As Studied by Solid-State NMR

2013 ◽  
Vol 117 (15) ◽  
pp. 7703-7712 ◽  
Author(s):  
Farhana Gul-E-Noor ◽  
Matthias Mendt ◽  
Dieter Michel ◽  
Andreas Pöppl ◽  
Harald Krautscheid ◽  
...  
Keyword(s):  
Solid State ◽  
Small Molecules ◽  
Solid State Nmr ◽  
Metal Organic Frameworks ◽  
Metal Organic

Solid-State NMR Applications in the Structural Elucidation of Small Molecules

2014 ◽  
pp. 173-240
Author(s):  
Mariana Sardo ◽  
João Rocha ◽  
Luís Mafra
Keyword(s):  
Solid State ◽  
Small Molecules ◽  
Solid State Nmr ◽  
Structural Elucidation

scholarly journals A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Vayu Maini Rekdal ◽  
Paola Nol Bernadino ◽  
Michael U Luescher ◽  
Sina Kiamehr ◽  
Chip Le ◽  
...  
Keyword(s):  
Small Molecules ◽  
Electron Acceptor ◽  
Molecular Basis ◽  
Distinct Group ◽  
Microbial Metabolism ◽  
Human Gut ◽  
Primary And Secondary Metabolism ◽  
Gut Microorganisms ◽  
Chemical Strategies ◽  
Mediate Metabolism

Catechol dehydroxylation is a central chemical transformation in the gut microbial metabolism of plant- and host-derived small molecules. However, the molecular basis for this transformation and its distribution among gut microorganisms are poorly understood. Here, we characterize a molybdenum-dependent enzyme from the human gut bacterium Eggerthella lenta that dehydroxylates catecholamine neurotransmitters. Our findings suggest that this activity enables E. lenta to use dopamine as an electron acceptor. We also identify candidate dehydroxylases that metabolize additional host- and plant-derived catechols. These dehydroxylases belong to a distinct group of largely uncharacterized molybdenum-dependent enzymes that likely mediate primary and secondary metabolism in multiple environments. Finally, we observe catechol dehydroxylation in the gut microbiotas of diverse mammals, confirming the presence of this chemistry in habitats beyond the human gut. These results suggest that the chemical strategies that mediate metabolism and interactions in the human gut are relevant to a broad range of species and habitats.

scholarly journals A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols

2019 ◽  
Author(s):  
Vayu Maini Rekdal ◽  
Paola Nol Bernardino ◽  
Michael U. Luescher ◽  
Sina Kiamehr ◽  
Peter J. Turnbaugh ◽  
...  
Keyword(s):  
Small Molecules ◽  
Molecular Basis ◽  
Distinct Group ◽  
Microbial Metabolism ◽  
Anaerobic Conditions ◽  
Human Gut ◽  
Primary And Secondary Metabolism ◽  
Gut Microorganisms ◽  
Chemical Strategies ◽  
Mediate Metabolism

AbstractCatechol dehydroxylation is a central chemical transformation in the gut microbial metabolism of plant- and host-derived small molecules. However, the molecular basis for this transformation and its distribution among gut microorganisms are poorly understood. Here, we characterize a molybdenum-dependent enzyme from the prevalent human gut bacteriumEggerthella lentathat specifically dehydroxylates catecholamine neurotransmitters available in the human gut. Our findings suggest that this activity enablesE. lentato use dopamine as an electron acceptor under anaerobic conditions. In addition to characterizing catecholamine dehydroxylation, we identify candidate molybdenum-dependent enzymes that dehydroxylate additional host-and plant-derived small molecules. These gut bacterial catechol dehydroxylases are specific in their substrate scope and transcriptional regulation and belong to a distinct group of largely uncharacterized molybdenum-dependent enzymes that likely mediate both primary and secondary metabolism in multiple environments. Finally, we observe catechol dehydroxylation in the gut microbiotas of diverse mammals, suggesting that this chemistry is present in habitats beyond the human gut. Altogether, our data reveal the molecular basis of catechol dehydroxylation among gut bacteria and suggest that the chemical strategies that mediate metabolism and interactions in the human gut are relevant to a broad range of species and habitats.

scholarly journals Towards a native environment: structure and function of membrane proteins in lipid bilayers by NMR

2021 ◽  
Author(s):  
Kai Xue ◽  
Kumar Tekwani Movellan ◽  
Xizhou Cecily Zhang ◽  
Eszter E. Najbauer ◽  
Marcel C. Forster ◽  
...  
Keyword(s):  
Solid State ◽  
Membrane Proteins ◽  
Small Molecules ◽  
Lipid Bilayers ◽  
Biological Samples ◽  
Solid State Nmr ◽  
Structure And Function ◽  
Versatile Technique ◽  
And Function

Solid-state NMR (ssNMR) is a versatile technique that can be used for the characterization of various materials, ranging from small molecules to biological samples, including membrane proteins, as reviewed here.

Postsynthetic modification of an imine-based microporous organic network

2011 ◽  
Vol 89 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Phillip A. Kerneghan ◽  
Shira D. Halperin ◽  
David L. Bryce ◽  
Kenneth E. Maly
Keyword(s):  
Solid State ◽  
Nmr Spectroscopy ◽  
Acetic Anhydride ◽  
Small Molecules ◽  
Solid State Nmr ◽  
Gas Adsorption ◽  
Guest Molecules ◽  
Adsorption Studies ◽  
Postsynthetic Modification ◽  
Enhanced Resistance

A highly cross-linked microporous organic network with imine linkers was prepared by condensation of tetrakis(4-aminophenyl)methane with terephthaldehyde. Gas adsorption studies indicate that the material exhibits permanent microporosity, and guest exchange experiments demonstrate that small molecules can diffuse into the network. Postsynthetic modification of this microporous network was achieved by treatment with borane in THF, which reduced the imine groups to the corresponding amines as shown by IR and 13C CP-MAS solid-state NMR spectroscopy. The resulting material showed enhanced resistance to acidic hydrolysis compared with the imine precursor, and retained its ability to absorb guest molecules. The amine network was amenable to further postsynthetic modifications. Specifically, acetylation of this network using acetic anhydride was demonstrated.

scholarly journals A Molecular Basis for Reciprocal Regulation between Pheromones and Hormones in Response to Dietary Cues in C. elegans

2020 ◽  
Vol 21 (7) ◽  
pp. 2366
Author(s):  
Saeram Park ◽  
Jun Young Park ◽  
Young-Ki Paik
Keyword(s):  
Gene Expression ◽  
Small Molecules ◽  
Molecular Basis ◽  
Biosynthetic Gene ◽  
Reciprocal Regulation ◽  
C Elegans ◽  
Aging Period ◽  
Transcriptional Regulatory ◽  
Dietary Cues ◽  
Development And Aging

Under stressful conditions, the early larvae of C. elegans enter dauer diapause, a non-aging period, driven by the seemingly opposite influence of ascaroside pheromones (ASCRs) and steroid hormone dafachronic acids (DAs). However, the molecular basis of how these small molecules engage in competitive crosstalk in coordination with insulin/IGF-1 signaling (IIS) remains elusive. Here we report a novel transcriptional regulatory pathway that seems to operate between the ASCR and DA biosynthesis under ad libitum (AL) feeding conditions or bacterial deprivation (BD). Although expression of the ASCR and DA biosynthetic genes reciprocally inhibit each other, ironically and interestingly, such dietary cue-mediated modulation requires the presence of the competitors. Under BD, induction of ASCR biosynthetic gene expression required DA, while ASCR suppresses the expression of the DA biosynthetic gene daf-36. The negative regulation of DA by ASCR was IIS-dependent, whereas daf-36 regulation appeared to be independent of IIS. These observations suggest that the presence of ASCR determines the IIS-dependency of DA gene expression regardless of dietary conditions. Thus, our work defines a molecular basis for a novel reciprocal gene regulation of pheromones and hormones to cope with stressful conditions during development and aging.

Exploring the structural landscape of 2-(thiophen-2-yl)-1,3-benzothiazole: high-Z′ packing polymorphism and cocrystallization with calix[4]tube

2019 ◽  
Vol 75 (6) ◽  
pp. 667-677 ◽  
Author(s):  
Meiry E. Alvarenga ◽  
Ana Karoline S. M. Valdo ◽  
Leandro Ribeiro ◽  
José Antonio Do Nascimento Neto ◽  
Debora P. De Araujo ◽  
...  
Keyword(s):  
Small Molecules ◽  
Dimethyl Sulfoxide ◽  
Inclusion Complexes ◽  
Sodium Ions ◽  
New Approach ◽  
Intermolecular Contacts ◽  
Simple Molecules ◽  
First Time ◽  
Guest Chemistry

We report here for the first time a cocrystal of the so-called neutral calix[4]tube, which is two tail-to-tail-arranged and partially deprotonated tetrakis(carboxymethoxy)calix[4]arenes, including three sodium ions, with 2-(thiophen-2-yl)-1,3-benzothiazole, namely trisodium bis(carboxymethoxy)bis(carboxylatomethoxy)calix[4]arene tris(carboxymethoxy)(carboxylatomethoxy)calix[4]arene–2-(thiophen-2-yl)-1,3-benzothiazole–dimethyl sulfoxide–water (1/1/2/2), 3Na+·C36H30O12 2−·C36H31O12 −·C11H7NS2·2C2H6OS·2H2O, which provides a new approach into the host–guest chemistry of inclusion complexes. Three packing polymorphs of the same benzothiazole with high Z′ (one with Z′ = 8 and two with Z′ = 4) were also discovered in the course of our desired cocrystallization. The inspection of these polymorphs and a previously known polymorph with Z′ = 2 revealed that Z′ increases as the strength of intermolecular contacts decreases. Also, these results expand the frontier of invoking calixarenes as a host for nonsolvent small molecules, besides providing knowledge on the rare formation of high-Z′ packing polymorphs of simple molecules, such as the target benzothiazole.

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