Cation-π bonding and amino-aromatic interactions in the biomolecular recognition of substituted ammonium ligands

Scrutton, Nigel S.; Raine, Andrew

doi:10.1042/bj3190001

Cited by 235 publications

(185 citation statements)

References 56 publications

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“…Indeed, the combination of three H-bonds and one cation-p interaction in a synthetic small molecule ammonium receptor has yielded micromolar affinity for NH 4 + and a selectivity of nearly 1,000 against K + [6]. The combination of these two types of interactions has also been noted in the biomolecular recognition of substituted ammonium ligands [35].…”

Section: Structure Of Amtb and Mechanistic Implicationsmentioning

confidence: 99%

Amt/MEP/Rh proteins conduct ammonia

Winkler

2005

Pflugers Arch - Eur J Physiol

110

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The structure determination of the ammonium transport protein AmtB from Escherichia coli strongly indicates that the members of the ubiquitous ammonium transporter/methylamine permease/Rhesus (Amt/ MEP/Rh) protein family are ammonia-conducting channels rather than ammonium ion transporters. The most conserved part of these proteins, apart from the common overall structure with 11 transmembrane helices, is the pore lined by hydrophobic side chains except for two highly conserved histidine residues. A highaffinity ion-binding site specific for ammonium is present at the extracellular pore entry of the Amt/MEP proteins. It is proposed to play an important role in enhancing net transport at very low external ammonium concentrations and to provide discrimination against water. The site is not conserved in the animal Rhesus proteins which are implicated in ammonium homeostasis and saturate at millimolar ammonium concentrations. Many aspects of the biological function of these ammonia channels are still poorly understood and further studies in cellular systems are needed. Likewise, studies with purified, reconstituted Amt/MEP/Rh proteins will be needed to resolve open mechanistic questions and gain a more quantitative understanding of the conduction mechanism in general and for different subfamily representatives.

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Section: Structure Of Amtb and Mechanistic Implicationsmentioning

confidence: 99%

Amt/MEP/Rh proteins conduct ammonia

Winkler

2005

Pflugers Arch - Eur J Physiol

110

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“…They were found in many systems and should be acknowledged as important non-covalent binding forces [81]. Cation-π interactions are highly competitive with other kinds of non-covalent bonding forces which are known as strong ones [82]. Since they are not only Bcationaromatic^relations, for fullerene molecules with 60 dislocated electrons, they should be a very important kind of contact with proteins.…”

Section: Characterization Of the Observed Fullerene C 60 -Protein Intmentioning

confidence: 99%

Rapid insight into C60 influence on biological functions of proteins

et al. 2017

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Experimental methods of investigations of nanoparticle (NP)-protein interactions are limited, because they require a high amount of samples and the NPs tend to interfere with spectral results. Therefore, molecular modeling is a commonly accepted tool in such kind of investigations. Examining the molecule toxicity on the molecular level, we usually want to know, mainly, the location of the ligand on the protein surface and what is an influence of such a contact on the biological functions of the protein. In the presented work, we demonstrate that multiple-docking of the ligand from a random start and with large grid volume, to let the ligand search the whole protein surface, allows to find the best binding sites and gives reliable results considering ligand-protein interactions. In the present work, we have constructed six models of bronchoalveolar lavage fluids proteins: α1-antitripsin, albumin, ceruloplasmin, lactoferrin, lysozyme, and transferrin with fullerene, C 60 utilizing molecular docking methods. The most probable results were examined with steered molecular dynamics (SMD) to see, if the simple docking method is able to predict the fullerene binding affinity. Albumin and lysozyme were already widely investigated and literature data is available for their complexes with fullerene C 60 and/or its derivatives. Thus, we used these two models as a reference set to validate the used molecular modeling methods. With our best knowledge, interactions of the remaining four proteins with NPs have never been investigated in detail before. Our results indicate that fullerene C 60 readily interacts with all studied proteins and may have a large impact on their biological functions.

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“…In proteins, cation-π interactions occur between the cationic side chain of lysine (K) or arginine (R) and the aromatic side chains of phenylalanine (F), tyrosine (Y) and tryptophan (W) (Chakravarty and Varadarajan, 2000). Previous studies on cation-π interactions have focused on various aspects such as their role in ligand recognition (Zacharias and Dougherty, 2002;Zhong et al, 1998;Scrutton and Raine, 1996) and protein drug interactions (Liu et al, 2002). There are several instances where cation-π interactions have shown to play a significant role.…”

Section: Introductionmentioning

confidence: 99%

“…The stability can be determined by several interactions such as salt bridge, di-sulfide bond, conventional hydrogen bonds electrostatic interaction, Van crucial in many areas of modern chemistry, especially in the field of molecular recognition and for structural stability (Hunter et al, 1990;Wintjens et al, 2000). In addition cation-π interaction (Dougherty, 1996; Ma and Dougherty, 1997; Scrutton and Raine, 1996) is increasingly recognized as an important noncovalent binding interaction relevant to structural biology.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of the Cation-π Interaction in Therapeutic Proteins: A Comparative Study with Conventional Stabilizing Forces

Shanthi¹,

Ramanathan²

2009

J Comput Sci Syst Biol

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The cation-π interaction is an important, general force for molecular recognition in biological receptors. In this study, we have analyzed the energy contribution resulting from cation-π interactions in the set of therapeutic proteins. The contribution of cation-π interacting residues in secondary structure involvement, solvent accessibility, stabilization centers, stabilizing residues and conservation score has been evaluated. Secondary structure of the cation-π involving residues shows that, Arg and Lys prefers to be in strand. Among the π residues, Phe prefer to be in coil, Tyr prefers to be in strand and Trp prefer to be in helix. Among the cation-π interacting residues Arg and Lys were in the exposed regions. Phe and Tyr were in the partially buried region and Trp in the fully buried region. Stabilization centers for these proteins showed that all the five residues found in cation-π interactions are important in locating one or more of such centers. The contribution of stabilizing residues in the cation-π interactions was analyzed. Further, the study shows that, 43 percent of the amino acid residues that are involved in cation-π interactions might be conserved in therapeutic proteins. The comparison between the conventional and nonconventional interactions in the data set, clearly depict the significance of cation-π interaction in the stability of therapeutic proteins. On the whole, the results presented in this work will be very useful for understanding the contribution of cation-π interaction to the stability of therapeutic proteins.

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Cation-π bonding and amino-aromatic interactions in the biomolecular recognition of substituted ammonium ligands

Cited by 235 publications

References 56 publications

Amt/MEP/Rh proteins conduct ammonia

Amt/MEP/Rh proteins conduct ammonia

Rapid insight into C60 influence on biological functions of proteins

Role of the Cation-π Interaction in Therapeutic Proteins: A Comparative Study with Conventional Stabilizing Forces

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