scholarly journals Structure and transport mechanism of the sodium/proton antiporter MjNhaP1

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Cristina Paulino ◽  
David Wöhlert ◽  
Ekaterina Kapotova ◽  
Özkan Yildiz ◽  
Werner Kühlbrandt
Keyword(s):  
Transport Mechanism ◽  
Ion Binding ◽  
Ph Homeostasis ◽  
Activity Maximum ◽  
X Ray ◽  
X Ray Crystallography ◽  
Highly Active ◽  
Health And Disease ◽  
Cooperative Transport ◽  
22Na Uptake

Sodium/proton antiporters are essential for sodium and pH homeostasis and play a major role in human health and disease. We determined the structures of the archaeal sodium/proton antiporter MjNhaP1 in two complementary states. The inward-open state was obtained by x-ray crystallography in the presence of sodium at pH 8, where the transporter is highly active. The outward-open state was obtained by electron crystallography without sodium at pH 4, where MjNhaP1 is inactive. Comparison of both structures reveals a 7° tilt of the 6 helix bundle. 22Na+ uptake measurements indicate non-cooperative transport with an activity maximum at pH 7.5. We conclude that binding of a Na+ ion from the outside induces helix movements that close the extracellular cavity, open the cytoplasmic funnel, and result in a ∼5 Å vertical relocation of the ion binding site to release the substrate ion into the cytoplasm.

scholarly journals Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Karthik Ramanadane ◽  
Monique S Straub ◽  
Raimund Dutzler ◽  
Cristina Manatschal
Keyword(s):  
Hydration Shell ◽  
Transition Metal Ions ◽  
Ion Binding ◽  
X Ray ◽  
X Ray Crystallography ◽  
Protein Architecture ◽  
Large Pool ◽  
Structural And Functional Properties ◽  
The Family ◽  
Magnesium Transporter

Members of the ubiquitous SLC11/NRAMP family catalyze the uptake of divalent transition metal ions into cells. They have evolved to efficiently select these trace elements from a large pool of Ca2+ and Mg2+, which are both orders of magnitude more abundant, and to concentrate them in the cytoplasm aided by the cotransport of H+ serving as energy source. In the present study, we have characterized a member of a distant clade of the family found in prokaryotes, termed NRMTs, that were proposed to function as transporters of Mg2+. The protein transports Mg2+ and Mn2+ but not Ca2+ by a mechanism that is not coupled to H+. Structures determined by cryo-EM and X-ray crystallography revealed a generally similar protein architecture compared to classical NRAMPs, with a restructured ion binding site whose increased volume provides suitable interactions with ions that likely have retained much of their hydration shell.

scholarly journals Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

2016 ◽  
Vol 12 ◽  
pp. 863-873 ◽  
Author(s):  
Shaojin Gu ◽  
Jiehao Du ◽  
Jingjing Huang ◽  
Huan Xia ◽  
Ling Yang ◽  
...  
Keyword(s):  
Room Temperature ◽  
Copper Complexes ◽  
Catalytic Properties ◽  
Polynuclear Complexes ◽  
Carbene Ligands ◽  
Efficient Catalyst ◽  
X Ray ◽  
X Ray Crystallography ◽  
Air Atmosphere ◽  
Highly Active

A series of copper complexes (3–6) stabilized by 1,2,3-triazole-tethered N-heterocyclic carbene ligands have been prepared via simple reaction of imidazolium salts with copper powder in good yields. The structures of bi- and trinuclear copper complexes were fully characterized by NMR, elemental analysis (EA), and X-ray crystallography. In particular, [Cu2(L2)2](PF6)2 (3) and [Cu2(L3)2](PF6)2 (4) were dinuclear copper complexes. Complexes [Cu3(L4)2](PF6)3 (5) and [Cu3(L5)2](PF6)3 (6) consist of a triangular Cu3 core. These structures vary depending on the imidazolium backbone and N substituents. The copper–NHC complexes tested are highly active for the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in an air atmosphere at room temperature in a CH3CN solution. Complex 4 is the most efficient catalyst among these polynuclear complexes in an air atmosphere at room temperature.

scholarly journals 6-Arylimino-2-(2-(1-phenylethyl)naphthalen-1-yl)-iminopyridylmetal (Fe and Co) Complexes as Highly Active Precatalysts for Ethylene Polymerization: Influence of Metal and/or Substituents on the Active, Thermostable Performance of Their Complexes and Resultant Polyethylenes

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4244 ◽  
Author(s):  
Wenhua Lin ◽  
Liping Zhang ◽  
Jiahao Gao ◽  
Qiuyue Zhang ◽  
Yanping Ma ◽  
...  
Keyword(s):  
Elevated Temperature ◽  
Single Crystal ◽  
Ethylene Polymerization ◽  
Active Species ◽  
Single Site ◽  
X Ray ◽  
X Ray Crystallography ◽  
Molecular Weights ◽  
Highly Active ◽  
Cobalt Center

A series of 6-arylimino-2-(2-(1-phenylethyl)naphthalen-1-yl)iminopyridines and their iron(II) and cobalt(II) complexes (Fe1–Fe5, Co1–Co5) were synthesized and routinely characterized as were Co3 and Co5 complexes, studied by single crystal X-ray crystallography, which individually displayed a distorted square pyramidal or trigonal bipyramid around a cobalt center. Upon treatment with either methyluminoxane (MAO) or modified methyluminoxane (MMAO), all complexes displayed high activities regarding ethylene polymerization even at an elevated temperature, enhancing the thermostability of the active species. In general, iron precatalysts showed higher activities than their cobalt analogs; for example, 10.9 × 106 g(PE) mol−1 (Co) h−1 by Co4 and 17.0 × 106 g(PE) mol−1 (Fe) h−1 by Fe4. Bulkier substituents are favored for increasing the molecular weights of the resultant polyethylenes, such as 25.6 kg mol−1 obtained by Co3 and 297 kg mol−1 obtained by Fe3. A narrow polydispersity of polyethylenes was observed by iron precatalysts activated by MMAO, indicating a single-site active species formed.

Current Breakthroughs in Structure-based Design of Synthetic and Natural Sourced Inhibitors Against Zika Viral Targets

2018 ◽  
Vol 18 (20) ◽  
pp. 1792-1803 ◽  
Author(s):  
Sisir Nandi ◽  
Ramandeep Kaur ◽  
Mohit Kumar ◽  
Ankita Sharma ◽  
Aaliya Naaz ◽  
...  
Keyword(s):  
Zika Virus ◽  
World Health ◽  
Health Concern ◽  
Mosquito Vector ◽  
Public Health Concern ◽  
Structure Based Drug Design ◽  
X Ray ◽  
X Ray Crystallography ◽  
Highly Active ◽  
Health Organization

Background: Zika is a worldwide pandemic dreadful viral transmission through Aedes mosquito vector. It significantly causes fever, joint pain or rash, and conjunctivitis. Pregnant mothers suffering from Zika viral infection may have fetal abnormalities due to severe neurological problems, characterized by microcephaly along with Guillain-Barré syndrome, issuing ZIKV a major public health concern as declared by the World Health Organization. There is hardly any FDA approved anti-Zika viral drugs available. Objective: Therefore, it is a big panic for the scientists to destroy the virus completely by generating potent inhibitors. Methods: For the purpose, various Zika viral targets were explored by structure-based design in the present review in connection with the discovery of various synthetic and natural sourced inhibitors against Zika virus. Results: The structure-based drug design tools such as x-ray crystallography and molecular docking reported various co-crystallized ligands and Zika virus inhibitors. Conclusion: Such inhibitors could further be modified for the design of highly active leads to combat Zika virus utilizing chemoinformatics modules.

scholarly journals Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography

2018 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Divalent Cation ◽  
Binding Sites ◽  
Divalent Cations ◽  
Cation Binding ◽  
Ion Binding ◽  
X Ray ◽  
High Ph ◽  
X Ray Crystallography ◽  
Ion Binding Sites

AbstractAcid sensing ion channels (ASICs) are proton-gated ion channels that are members of the degenerin/epithelial sodium channel superfamily and are expressed throughout central and peripheral nervous systems. ASICs have been implicated in multiple physiological processes and are subject to numerous forms of endogenous and exogenous regulation that include modulation by Ca2+ and Cl− ions. However, the mapping of ion binding sites as well as a structure-based understanding of the mechanisms underlying ionic modulation of ASICs have remained elusive. Here we present ion binding sites of chicken ASIC1a in resting and desensitized states at high and low pH, respectively, determined by anomalous diffraction x-ray crystallography. The acidic pocket serves as a nexus for divalent cation binding at both low and high pH, while we observe divalent cation binding within the central vestibule on the resting channel at high pH only. Moreover, neutralization of residues positioned to coordinate divalent cations via individual and combined Glu to Gln substitutions reduced, but did not extinguish, modulation of proton-dependent gating by Ca2+. Additionally, we demonstrate that anion binding at the canonical thumb domain site is state-dependent and present a previously undetected anion site at the mouth of the extracellular fenestrations on the resting channel. Our results map anion and cation sites on ASICs across multiple functional states, informing possible mechanisms of modulation and providing a blueprint for the design of therapeutics targeting ASICs.

scholarly journals Structural and functional properties of a magnesium transporter of the SLC11/NRAMP family

2021 ◽  
Author(s):  
Karthik Ramanadane ◽  
Monique S Straub ◽  
Raimund Dutzler ◽  
Cristina Manatschal
Keyword(s):  
Hydration Shell ◽  
Transition Metal Ions ◽  
Ion Binding ◽  
X Ray ◽  
X Ray Crystallography ◽  
Protein Architecture ◽  
Large Pool ◽  
Structural And Functional Properties ◽  
The Family ◽  
Magnesium Transporter

Members of the ubiquitous SLC11/NRAMP family catalyze the uptake of divalent transition metal ions into cells. They have evolved to efficiently select these trace elements from a large pool of Ca2+ and Mg2+, which are both orders of magnitude more abundant, and to concentrate them in the cytoplasm aided by the cotransport of H+ serving as energy source. In the present study, we have characterized a member of a distant clade of the family found in prokaryotes, termed NRMTs, that were proposed to function as transporters of Mg2+. The protein transports Mg2+ and Mn2+ but not Ca2+ by a mechanism that is not coupled to H+. Structures determined by cryo-EM and X-ray crystallography revealed a generally similar protein architecture compared to classical NRAMPs, with a restructured ion binding site whose increased volume provides suitable interactions with ions that likely have retained much of their hydration shell.

The transport mechanism of P4 ATPase lipid flippases

2020 ◽  
Vol 477 (19) ◽  
pp. 3769-3790
Author(s):  
Rosa L. López-Marqués ◽  
Pontus Gourdon ◽  
Thomas Günther Pomorski ◽  
Michael Palmgren
Keyword(s):  
Transport Mechanism ◽  
Structural Models ◽  
Lipid Transport ◽  
Specific Lipids ◽  
Specific Expression ◽  
X Ray ◽  
X Ray Crystallography ◽  
Cellular Processes ◽  
Order Of Magnitude ◽  
Intense Debate

P4 ATPase lipid flippases are ATP-driven transporters that translocate specific lipids from the exoplasmic to the cytosolic leaflet of biological membranes, thus establishing a lipid gradient between the two leaflets that is essential for many cellular processes. While substrate specificity, subcellular and tissue-specific expression, and physiological functions have been assigned to a number of these transporters in several organisms, the mechanism of lipid transport has been a topic of intense debate in the field. The recent publication of a series of structural models based on X-ray crystallography and cryo-EM studies has provided the first glimpse into how P4 ATPases have adapted the transport mechanism used by the cation-pumping family members to accommodate a substrate that is at least an order of magnitude larger than cations.

Ion-Mediated Electron Transfer in a Supramolecular Donor-Acceptor Ensemble

Science ◽  
2010 ◽  
Vol 329 (5997) ◽  
pp. 1324-1327 ◽  
Author(s):  
Jung Su Park ◽  
Elizabeth Karnas ◽  
Kei Ohkubo ◽  
Ping Chen ◽  
Karl M. Kadish ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Ion Binding ◽  
Acceptor Pair ◽  
Initial Oxidation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Back Electron Transfer ◽  
Donor And Acceptor ◽  
Mediated Electron Transfer ◽  
Donor Acceptor

Ion binding often mediates electron transfer in biological systems as a cofactor strategy, either as a promoter or as an inhibitor. However, it has rarely, if ever, been exploited for that purpose in synthetic host-guest assemblies. We report here that strong binding of specific anions (chloride, bromide, and methylsulfate but not tetrafluoroborate or hexafluorophosphate) to a tetrathiafulvalene calix[4]pyrrole (TTF-C4P) donor enforces a host conformation that favors electron transfer to a bisimidazolium quinone (BIQ2+) guest acceptor. In contrast, the addition of a tetraethylammonium cation, which binds more effectively than the BIQ2+ guest in the TTF-C4P cavity, leads to back electron transfer, restoring the initial oxidation states of the donor and acceptor pair. The products of these processes were characterized via spectroscopy and x-ray crystallography.

Difference Fourier Analysis of Glucose Embedded and Frozen Hydrated Purple Membrane

1982 ◽  
Vol 40 ◽  
pp. 74-75
Author(s):  
Jules S. Jaffe ◽  
Robert M. Glaeser
Keyword(s):  
Purple Membrane ◽  
Data Set ◽  
High Resolution Data ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fourier Techniques ◽  
Versus Protein ◽  
The Difference ◽  
Difference Fourier ◽  
Ideal Method

Although difference Fourier techniques are standard in X-ray crystallography it has only been very recently that electron crystallographers have been able to take advantage of this method. We have combined a high resolution data set for frozen glucose embedded Purple Membrane (PM) with a data set collected from PM prepared in the frozen hydrated state in order to visualize any differences in structure due to the different methods of preparation. The increased contrast between protein-ice versus protein-glucose may prove to be an advantage of the frozen hydrated technique for visualizing those parts of bacteriorhodopsin that are embedded in glucose. In addition, surface groups of the protein may be disordered in glucose and ordered in the frozen state. The sensitivity of the difference Fourier technique to small changes in structure provides an ideal method for testing this hypothesis.

3-D reconstruction of molecular shape from microcrystal thin sections

1983 ◽  
Vol 41 ◽  
pp. 748-749
Author(s):  
S. Cusack ◽  
J.-C. Jésior
Keyword(s):  
Three Dimensional ◽  
Molecular Shape ◽  
Biological Molecules ◽  
Fourier Space ◽  
Single Particles ◽  
Thin Sections ◽  
Standard Methods ◽  
X Ray ◽  
X Ray Crystallography ◽  
Dimensional Reconstruction

Three-dimensional reconstruction techniques using electron microscopy have been principally developed for application to 2-D arrays (i.e. monolayers) of biological molecules and symmetrical single particles (e.g. helical viruses). However many biological molecules that crystallise form multilayered microcrystals which are unsuitable for study by either the standard methods of 3-D reconstruction or, because of their size, by X-ray crystallography. The grid sectioning technique enables a number of different projections of such microcrystals to be obtained in well defined directions (e.g. parallel to crystal axes) and poses the problem of how best these projections can be used to reconstruct the packing and shape of the molecules forming the microcrystal.Given sufficient projections there may be enough information to do a crystallographic reconstruction in Fourier space. We however have considered the situation where only a limited number of projections are available, as for example in the case of catalase platelets where three orthogonal and two diagonal projections have been obtained (Fig. 1).

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