scholarly journals Probing the conformation of a conserved glutamic acid within the Cl− pathway of a CLC H+/Cl− exchanger

2017 ◽  
Vol 149 (4) ◽  
pp. 523-529 ◽  
Author(s):  
Malvin Vien ◽  
Daniel Basilio ◽  
Lilia Leisle ◽  
Alessio Accardi
Keyword(s):  
Hydrogen Bonds ◽  
Glutamic Acid ◽  
Transport Proteins ◽  
Side Chain ◽  
Ion Binding ◽  
Computational Studies ◽  
Transport Models ◽  
Ions Transport ◽  
Selective Transport ◽  
Transport Cycle

The CLC proteins form a broad family of anion-selective transport proteins that includes both channels and exchangers. Despite extensive structural, functional, and computational studies, the transport mechanism of the CLC exchangers remains poorly understood. Several transport models have been proposed but have failed to capture all the key features of these transporters. Multiple CLC crystal structures have suggested that a conserved glutamic acid, Gluex, can adopt three conformations and that the interconversion of its side chain between these states underlies H+/Cl− exchange. One of these states, in which Gluex occupies the central binding site (Scen) while Cl− ions fill the internal and external sites (Sint and Sext), has only been observed in one homologue, the eukaryotic cmCLC. The existence of such a state in other CLCs has not been demonstrated. In this study, we find that during transport, the prototypical prokaryotic CLC exchanger, CLC-ec1, adopts a conformation with functional characteristics that match those predicted for a cmCLC-like state, with Gluex trapped in Scen between two Cl− ions. Transport by CLC-ec1 is reduced when [Cl−] is symmetrically increased on both sides of the membrane and mutations that disrupt the hydrogen bonds stabilizing Gluex in Scen destabilize this trapped state. Furthermore, inhibition of transport by high [Cl−] is abolished in the E148A mutant, in which the Gluex side chain is removed. Collectively, our results suggest that, during the CLC transport cycle, Gluex can occupy Scen as well as the Sext position in which it has been captured crystallographically and that hydrogen bonds with the side chains of residues that coordinate ion binding to Scen play a role in determining the equilibrium between these two conformations.

Side chain-backbone hydrogen bonds in peptides containing glutamic acid residues

Biopolymers ◽  
1979 ◽  
Vol 18 (5) ◽  
pp. 1293-1296 ◽  
Author(s):  
Roger Mayer ◽  
G�rard Lancelot ◽  
G�rard Spach
Keyword(s):  
Hydrogen Bonds ◽  
Glutamic Acid ◽  
Side Chain

scholarly journals Effects of Amino Acid Side-Chain Length and Chemical Structure on Anionic Polyglutamic and Polyaspartic Acid Cellulose-Based Polyelectrolyte Brushes

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1789
Author(s):  
Dmitry Tolmachev ◽  
George Mamistvalov ◽  
Natalia Lukasheva ◽  
Sergey Larin ◽  
Mikko Karttunen
Keyword(s):  
Glutamic Acid ◽  
Chain Length ◽  
Chemical Structure ◽  
Side Chain ◽  
Side Chains ◽  
Side Chain Length ◽  
Polyelectrolyte Brushes ◽  
Grafting Density ◽  
The Difference ◽  
Cellulose Surface

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α,L-glutamic acid and α,L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is to search for ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side-chain length, the chemical structure and their interplay are required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side-chain rotation, enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side-chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main-chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

Bifurcated Hydrogen Bonds Stabilize Fibrils of Poly(l-glutamic) Acid

2010 ◽  
Vol 114 (24) ◽  
pp. 8278-8283 ◽  
Author(s):  
Aleksandra Fulara ◽  
Wojciech Dzwolak
Keyword(s):  
Hydrogen Bonds ◽  
Glutamic Acid

WHICH IS THE PROTON-SHUTTLE IN ISOXANTHOPTERIN DEAMINASE? QM/MM MD UNDERSTANDING

2013 ◽  
Vol 12 (08) ◽  
pp. 1341002 ◽  
Author(s):  
XIN ZHANG ◽  
MING LEI
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Hydrogen Bonds ◽  
Proton Transfer ◽  
Glutamic Acid ◽  
Active Site ◽  
Nucleophilic Attack ◽  
Zinc Ions ◽  
Initial Model ◽  
Dynamics Simulations

The deamination process of isoxanthopterin catalyzed by isoxanthopterin deaminase was determined using the combined QM(PM3)/MM molecular dynamics simulations. In this paper, the updated PM3 parameters were employed for zinc ions and the initial model was built up based on the crystal structure. Proton transfer and following steps have been investigated in two paths: Asp336 and His285 serve as the proton shuttle, respectively. Our simulations showed that His285 is more effective than Aap336 in proton transfer for deamination of isoxanthopterin. As hydrogen bonds between the substrate and surrounding residues play a key role in nucleophilic attack, we suggested mutating Thr195 to glutamic acid, which could enhance the hydrogen bonds and help isoxanthopterin get close to the active site. The simulations which change the substrate to pterin 6-carboxylate also performed for comparison. Our results provide reference for understanding of the mechanism of deaminase and for enhancing the deamination rate of isoxanthopterin deaminase.

Infrared Studies of the Side-Chain Orientation in Solid Films of Esters of Poly(L-glutamic acid)

1973 ◽  
Vol 6 (5) ◽  
pp. 780-785 ◽  
Author(s):  
M. Delporte-Leroy ◽  
P. Le Barny ◽  
M. H. Loucheux-Lefebvre
Keyword(s):  
Glutamic Acid ◽  
Side Chain ◽  
Chain Orientation ◽  
Solid Films ◽  
Infrared Studies ◽  
Side Chain Orientation

Thermal-induced transformation of glutamic acid to pyroglutamic acid and self-cocrystallization: a charge–density analysis

2022 ◽  
Vol 78 (2) ◽  
Author(s):  
Sehrish Akram ◽  
Arshad Mehmood ◽  
Sajida Noureen ◽  
Maqsood Ahmed
Keyword(s):  
Hydrogen Bonds ◽  
Glutamic Acid ◽  
Single Crystal ◽  
Diffraction Data ◽  
Density Functional ◽  
Quantitative Estimation ◽  
Topological Analysis ◽  
Pyroglutamic Acid ◽  
X Ray Diffraction ◽  
X Ray

Thermal-induced transformation of glutamic acid to pyroglutamic acid is well known. However, confusion remains over the exact temperature at which this happens. Moreover, no diffraction data are available to support the transition. In this article, we make a systematic investigation involving thermal analysis, hot-stage microscopy and single-crystal X-ray diffraction to study a one-pot thermal transition of glutamic acid to pyroglutamic acid and subsequent self-cocrystallization between the product (hydrated pyroglutamic acid) and the unreacted precursor (glutamic acid). The melt upon cooling gave a robust cocrystal, namely, glutamic acid–pyroglutamic acid–water (1/1/1), C5H7NO3·C5H9NO4·H2O, whose structure has been elucidated from single-crystal X-ray diffraction data collected at room temperature. A three-dimensional network of strong hydrogen bonds has been found. A Hirshfeld surface analysis was carried out to make a quantitative estimation of the intermolecular interactions. In order to gain insight into the strength and stability of the cocrystal, the transferability principle was utilized to make a topological analysis and to study the electron-density-derived properties. The transferred model has been found to be superior to the classical independent atom model (IAM). The experimental results have been compared with results from a multipolar refinement carried out using theoretical structure factors generated from density functional theory (DFT) calculations. Very strong classical hydrogen bonds drive the cocrystallization and lend stability to the resulting cocrystal. Important conclusions have been drawn about this transition.

scholarly journals Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps

2014 ◽  
Vol 143 (4) ◽  
pp. 449-464 ◽  
Author(s):  
Natascia Vedovato ◽  
David C. Gadsby
Keyword(s):  
Binding Site ◽  
Single Molecule ◽  
Conformational Changes ◽  
Outward Current ◽  
Side Chain ◽  
Ion Binding ◽  
Inward Current ◽  
Na Release ◽  
K Transport ◽  
External K

A single Na+/K+-ATPase pumps three Na+ outwards and two K+ inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na+ than K+ generates outward current across the cell membrane. Less well understood is the ability of Na+/K+ pumps to generate an inward current of protons. Originally noted in pumps deprived of external K+ and Na+ ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K+ and Na+ concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na+ release from phosphorylated Na+/K+ pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na+/K+ pumps that enables proton import is not required for completion of the 3 Na+/2 K+ transport cycle. However, the back-step occurs readily during Na+/K+ transport when external K+ ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na+-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na+ and K+ ions that passes through binding site II. The inferred occurrence of Na+/K+ exchange and H+ import during the same conformational cycle of a single molecule identifies the Na+/K+ pump as a hybrid transporter. Whether Na+/K+ pump–mediated proton inflow may have any physiological or pathophysiological significance remains to be clarified.

scholarly journals Diethyl (E)-2,3-bis[(E)-(2-methyl-2-phenylhydrazin-1-ylidene)methyl]but-2-enedioate

2014 ◽  
Vol 70 (6) ◽  
pp. o723-o723
Author(s):  
Peng Liu ◽  
Libin Yuan ◽  
Xiuqing Song ◽  
Hong Yan
Keyword(s):  
Hydrogen Bonds ◽  
Title Compound ◽  
Phenyl Ring ◽  
Side Chain ◽  
Dihedral Angles ◽  
Inversion Symmetry ◽  
Compound C ◽  
Corrugated Sheets ◽  
Major Conformation

The complete molecule of the title compound, C24H28N4O4, is generated by crystallographic inversion symmetry. The ethyl side chain is disordered over two sets of sites in a 0.57 (4):0.43 (4) ratio. The dihedral angles between the methylidene group and the phenyl ring and ester side chain (major conformation) are 7.61 (8) and 86.95 (8)°, respectively. In the crystal, molecules are linkedviaC—H...O hydrogen bonds, forming corrugated sheets lying parallel to (010).

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