scholarly journals Structure Modeling of the Norepinephrine Transporter

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 102 ◽  
Author(s):  
Izabella Góral ◽  
Kamil Łątka ◽  
Marek Bajda
Keyword(s):  
Aspartic Acid ◽  
Molecular Orientation ◽  
Binding Pocket ◽  
Norepinephrine Transporter ◽  
Structure Modeling ◽  
Monoamine Transporters ◽  
Extracellular Loop ◽  
Peripheral Nervous System Diseases ◽  
X Ray ◽  
Related Proteins

The norepinephrine transporter (NET) is one of the monoamine transporters. Its X-ray crystal structure has not been obtained yet. Inhibitors of human NET (hNET) play a major role in the treatment of many central and peripheral nervous system diseases. In this study, we focused on the spatial structure of a NET constructed by homology modeling on Drosophila melanogaster dopamine transporter templates. We further examined molecular construction of primary binding pocket (S1) together with secondary binding site (S2) and extracellular loop 4 (EL4). The next stage involved docking of transporter inhibitors: Reboxetine, duloxetine, desipramine, and other commonly used drugs. The procedure revealed the molecular orientation of residues and disclosed ones that are the most important for ligand binding: Phenylalanine F72, aspartic acid D75, tyrosine Y152, and phenylalanine F317. Aspartic acid D75 plays a key role in recognition of the basic amino group present in monoamine transporter inhibitors and substrates. The study also presents a comparison of hNET models with other related proteins, which could provide new insights into their interaction with therapeutics and aid future development of novel bioactive compounds.

scholarly journals Structural basis of norepinephrine recognition and transport inhibition in neurotransmitter transporters

2020 ◽  
Author(s):  
Shabareesh Pidathala ◽  
Aditya Kumar Mallela ◽  
Deepthi Joseph ◽  
Aravind Penmatsa
Keyword(s):  
Chronic Pain ◽  
Binding Site ◽  
Dopamine Transporter ◽  
Binding Pocket ◽  
Norepinephrine Transporter ◽  
Structural Basis ◽  
List Type ◽  
X Ray ◽  
Neurotransmitter Transporters ◽  
Reuptake Inhibition

AbstractNorepinephrine is a biogenic amine neurotransmitter that has widespread effects on cardiovascular tone, alertness and sensation of pain. As a consequence, blockers of norepinephrine uptake have served as vital tools to treat depression and chronic pain. Here, we employ a modified Drosophila melanogaster dopamine transporter as a surrogate for the human norepinephrine transporter and determine the X-ray structures of the transporter in its substrate-free and norepinephrine-bound forms. We also report structures of the transporter in complex with inhibitors of chronic pain including duloxetine, milnacipran and a synthetic opioid, tramadol. When compared to dopamine, we observe that norepinephrine binds in a different pose, in the vicinity of subsite C within the primary binding site. Our experiments reveal that this region is the binding site for chronic pain inhibitors and a determinant for norepinephrine-specific reuptake inhibition, thereby providing a paradigm for the design of specific inhibitors for catecholamine neurotransmitter transporters.HighlightsX-ray structures of the Drosophila dopamine transporter in substrate-free and norepinephrine bound forms.Norepinephrine and dopamine bind in distinct conformations within the binding pocket.Chronic pain inhibitors S-duloxetine, milnacipran and tramadol bind in the primary binding site and overlap with the norepinephrine-binding pose.Selective norepinephrine reuptake inhibition occurs through specific interactions at the subsite C in the primary binding pocket.

scholarly journals Zeolite NaP1 Functionalization for the Sorption of Metal Complexes with Biodegradable N-(1,2-dicarboxyethyl)-D,L-aspartic Acid

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2518
Author(s):  
Dorota Kołodyńska ◽  
Yongming Ju ◽  
Małgorzata Franus ◽  
Wojciech Franus
Keyword(s):  
Experimental Data ◽  
Aspartic Acid ◽  
Ph Value ◽  
Complexing Agents ◽  
X Ray Diffraction ◽  
Experimental Conditions ◽  
Modified Zeolite ◽  
X Ray ◽  
Slow Release Fertilizers ◽  
Pseudo Second Order

The possibility of application of chitosan-modified zeolite as sorbent for Cu(II), Zn(II), Mn(II), and Fe(III) ions and their mixtures in the presence of N-(1,2-dicarboxyethyl)-D,L-aspartic acid, IDHA) under different experimental conditions were investigated. Chitosan-modified zeolite belongs to the group of biodegradable complexing agents used in fertilizer production. NaP1CS as a carrier forms a barrier to the spontaneous release of the fertilizer into soil. The obtained materials were characterized by Fourier transform infrared spectroscopy (FTIR); surface area determination (ASAP); scanning electron microscopy (SEM-EDS); X-ray fluorescence (XRF); X-ray diffraction (XRD); and carbon, hydrogen, and nitrogen (CHN), as well as thermogravimetric (TGA) methods. The concentrations of Cu(II), Zn(II), Mn(II), and Fe(III) complexes with IDHA varied from 5–20 mg/dm3 for Cu(II), 10–40 mg/dm3 for Fe(III), 20–80 mg/dm3 for Mn(II), and 10–40 mg/dm3 for Zn(II), respectively; pH value (3–6), time (1–120 min), and temperature (293–333 K) on the sorption efficiency were tested. The Langmuir, Freundlich, Dubinin–Radushkevich, and Temkin adsorption models were applied to describe experimental data. The pH 5 proved to be appropriate for adsorption. The pseudo-second order and Langmuir models were consistent with the experimental data. The thermodynamic parameters indicate that adsorption is spontaneous and endothermic. The highest desorption percentage was achieved using the HCl solution, therefore, proving that method can be used to design slow-release fertilizers.

scholarly journals X-ray crystallography reveals molecular recognition mechanism for sugar binding in a melibiose transporter MelB

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lan Guan ◽  
Parameswaran Hariharan
Keyword(s):  
Molecular Recognition ◽  
Binding Pocket ◽  
Cation Binding ◽  
Recognition Mechanism ◽  
X Ray ◽  
X Ray Crystallography ◽  
Sugar Binding ◽  
Sugar Specificity ◽  
Major Facilitator ◽  
Mfs Transporters

AbstractMajor facilitator superfamily_2 transporters are widely found from bacteria to mammals. The melibiose transporter MelB, which catalyzes melibiose symport with either Na+, Li+, or H+, is a prototype of the Na+-coupled MFS transporters, but its sugar recognition mechanism has been a long-unsolved puzzle. Two high-resolution X-ray crystal structures of a Salmonella typhimurium MelB mutant with a bound ligand, either nitrophenyl-α-d-galactoside or dodecyl-β-d-melibioside, were refined to a resolution of 3.05 or 3.15 Å, respectively. In the substrate-binding site, the interaction of both galactosyl moieties on the two ligands with MelBSt are virturally same, so the sugar specificity determinant pocket can be recognized, and hence the molecular recognition mechanism for sugar binding in MelB has been deciphered. The conserved cation-binding pocket is also proposed, which directly connects to the sugar specificity pocket. These key structural findings have laid a solid foundation for our understanding of the cooperative binding and symport mechanisms in Na+-coupled MFS transporters, including eukaryotic transporters such as MFSD2A.

Template Induced Synthesis of Nano-Hydroxyapatite by Co-Precipitation Method

2011 ◽  
Vol 311-313 ◽  
pp. 1713-1716 ◽  
Author(s):  
Yan Rong Sun ◽  
Tao Fan ◽  
Chang An Wang ◽  
Li Guo Ma ◽  
Feng Liu
Keyword(s):  
Electron Microscope ◽  
Chondroitin Sulfate ◽  
Aspartic Acid ◽  
Transmission Electron Microscope ◽  
Precipitation Method ◽  
X Ray Diffraction ◽  
X Ray ◽  
Structure And Morphology ◽  
Transmission Electron ◽  
Co Precipitation

Nano-hydroxyapatite with different morphology was synthesized by the co-precipitation method coupled with biomineralization using Ca(NO3)2•4H2O and (NH4)2HPO4 as reagents, adding chondroitin sulfate, agarose and aspartic acid as template. The structure and morphology of the prepared powders were characterized by X-ray diffraction (XRD) and transmission electron microscope (TEM).

Study of the distribution of the molecular orientation in thick polyethylene samples by X-ray diffraction, infra-red dichroism and Raman spectroscopy

Polymer ◽  
1993 ◽  
Vol 34 (24) ◽  
pp. 5029-5037 ◽  
Author(s):  
Claude-Paul Lafrance ◽  
Paul Chabot ◽  
Marie Pigeon ◽  
Robert E Prud'homme ◽  
Michel Pézolet
Keyword(s):  
Raman Spectroscopy ◽  
Molecular Orientation ◽  
X Ray Diffraction ◽  
X Ray ◽  
Infra Red

Mapping Surface Chemistry and Molecular Orientation with Combinatorial Near-Edge X-Ray Absorption Fine Structure Spectroscopy

2004 ◽  
Vol 25 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Daniel A. Fischer ◽  
Kirill Efimenko ◽  
Rajendra R. Bhat ◽  
Sharadha Sambasivan ◽  
Jan Genzer
Keyword(s):  
Fine Structure ◽  
Surface Chemistry ◽  
Molecular Orientation ◽  
X Ray ◽  
Absorption Fine ◽  
X Ray Absorption

Determination of preferential molecular orientation in porphyrin-fullerene dyad ZnDHD6ee monolayers by the X-ray standing-wave method and X-ray reflectometry

2013 ◽  
Vol 58 (6) ◽  
pp. 934-938 ◽  
Author(s):  
A. Yu. Seregin ◽  
Yu. A. D’yakova ◽  
S. N. Yakunin ◽  
I. A. Makhotkin ◽  
A. S. Alekseev ◽  
...  
Keyword(s):  
Standing Wave ◽  
Molecular Orientation ◽  
Wave Method ◽  
X Ray ◽  
Standing Wave Method

X-ray structures of ferritins and related proteins

2010 ◽  
Vol 1800 (8) ◽  
pp. 706-718 ◽  
Author(s):  
Robert R. Crichton ◽  
Jean-Paul Declercq
Keyword(s):  
X Ray ◽  
Related Proteins
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