Simple Cation−π Interaction between a Phenyl Ring and a Protonated Amine Stabilizes an α-Helix in Water

Tsou, Lun K.; Tatko, Chad D.; Waters, Marcey L.

doi:10.1021/ja026721a

Cited by 100 publications

(80 citation statements)

References 40 publications

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“…Similar hydrophobic interactions between lysine and glutamic acid have been observed in related coiled-coil systems. [23,24] NMR structure calculation: The calculation of NMR solution structures was undertaken to further confirm our experimental observations. By using the program CNSSolve, a simulated annealing protocol was used in conjuction with NMR chemical shift and NOE data to generate a number of low-energy structures for the b-hairpins WKL and WKMe 3 L. [25] Shown below are selected 10 lowest-energy structures from the simulated annealing runs (Figure 13).…”

mentioning

confidence: 86%

Effects of Chain Length and N‐Methylation on a Cation–π Interaction in a β‐Hairpin Peptide

Hughes

Benshoff

Waters

2007

Chemistry A European J

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The effects of N-methylation and chain length on a cation-pi interaction have been investigated within the context of a beta-hairpin peptide. Significant enhancement of the interaction and structural stabilization of the hairpin have been observed upon Lys methylation. Thermodynamic analysis indicates an increased entropic driving force for folding upon methylation of Lys residues. Comparison of lysine to analogues ornithine (Orn) and diaminobutyric acid (Dab) indicates that lysine provides the strongest cation-pi interaction and also provides the most stable beta-hairpin due to a combination of side chain-side chain interactions and beta-sheet propensities. These studies have significance for the recognition of methylated lysine in histone proteins.

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mentioning

confidence: 86%

Effects of Chain Length and N‐Methylation on a Cation–π Interaction in a β‐Hairpin Peptide

Hughes

Benshoff

Waters

2007

Chemistry A European J

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“…Perhaps the EDC cross-linking in the presence of diC 7 PC micelles traps most of the protein with the rim tryptophans in this orientation. The energetics for interaction of a specific PC molecule with each tryptophan could be -cation stacking as observed in peptide systems (32), but here the positively charged choline N(CH 3 ) 3 substitutes for the lysine or arginine cationic moiety. The tryptophan-diC 7 PC complex would then be poised for more extensive interactions with a zwitterionic surface.…”

Section: Discussionmentioning

confidence: 99%

Cross-linking Phosphatidylinositol-specific Phospholipase C Traps Two Activating Phosphatidylcholine Molecules on the Enzyme

Zhang

Wehbi

Roberts

2004

Journal of Biological Chemistry

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Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (PI-PLC), a bacterial model for the catalytic domain of mammalian PI-PLC enzymes, was cross-linked by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride to probe for the aggregation and/or conformational changes of PI-PLC when bound to activating phosphatidylcholine (PC) interfaces. Dimers and higher order multimers (up to 31% of the total protein when cross-linked at pH 7) were observed when the enzyme was cross-linked in the presence of PC vesicles. Aggregates were also detected with PI-PLC bound to diheptanoyl-PC (diC 7 PC) micelles, although the fraction of cross-linked multimers (19% at pH 7) was lower than when the enzyme was cross-linked in the presence of vesicles. PI-PLC cross-linked in the presence of a diC 7 PC interface exhibited an enhanced specific activity for PI cleavage. The extent of this crosslinking-enhanced activation was reduced in PI-PLC mutants lacking either tryptophan in the rim (W47A and W242A) of this (␤␣) 8 -barrel protein. The higher activity of the native protein cross-linked in the presence of diC 7 PC correlated with an increased affinity of the protein for two diC 7 PC molecules as detected by matrixassisted laser desorption-ionization time-of-flight mass spectrometry. In contrast to wild type protein, W47A and W242A had only a single diC 7 PC tightly associated when cross-linked in the presence of that activator molecule. These results indicate that (i) each rim tryptophan residue is involved in binding a PC molecule at interfaces, (ii) the affinity of the enzyme for an activating PC molecule is enhanced when the protein is bound to a surface, and (iii) this conformation of the enzyme with at least two PC bound that is stabilized by chemical cross-linking interacts more effectively with activating interfaces, leading to higher observed specific activities for the phosphotransferase reaction.

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“…Altogether, the data support: 1) a nondiscriminating role of Asp-129 and Tyr-197 in the recognition of the NH main chain of the MetSO with the amino and carboxyl groups of MetSO either free, and thus, charged, or engaged in amide bonds, as is the case for a protein-bound MetSO; and 2) a higher contribution of Asp-129 to the substrate binding when compared with . Nevertheless, the fact that a phenyl ring can make interaction with a peptidic bond as well as with a protonated amine (21,22) prevents discrimination between a direct role of Tyr-197 in substrate binding or an indirect role, via the orientation of the carboxylate group of Asp-129. Anyway, the contribution of Asp-129 and Tyr-197 remains modest when compared with that of Phe-52 and Trp-53 in terms of K S values.…”

Section: Role Of Asp-129 and Tyr-197 In The Recognition Of The Main Cmentioning

confidence: 99%

Characterization of the Amino Acids Involved in Substrate Specificity of Methionine Sulfoxide Reductase A

Gand¹,

Antoine²,

Boschi‐Muller³

et al. 2007

Journal of Biological Chemistry

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Methionine sulfoxide reductases (Msrs) are ubiquitous enzymes that catalyze the thioredoxin-dependent reduction of methionine sulfoxide (MetSO) back to methionine. In vivo, Msrs are essential in protecting cells against oxidative damages on proteins and in the virulence of some bacteria. There exists two structurally unrelated classes of Msrs. MsrAs are stereo-specific toward the S epimer on the sulfur of the sulfoxide, whereas MsrBs are specific toward the R isomer. Both classes of Msrs display a similar catalytic mechanism of sulfoxide reduction by thiols via the sulfenic acid chemistry and a better affinity for protein-bound MetSO than for free MetSO. Recently, the role of the amino acids implicated in the catalysis of the reductase step of Neisseria meningitidis MsrA was determined. In the present study, the invariant amino acids potentially involved in substrate binding, i. Methionine is one of the amino acids in proteins that is the most sensitive to reactive oxygen species (1). It is converted into methionine sulfoxide (MetSO), 2 the function of which is a mixture of two epimers at the sulfur atom, i.e. Met-S-SO and Met-R-SO (2). Formation of MetSO may impair the biological function of the oxidized proteins, depending on the location of the MetSO in the protein. There exist two structurally unrelated classes of methionine sulfoxide reductases (Msrs) in most organisms, called MsrA and MsrB, which selectively reduce free or protein-bound Met-S-SO and Met-R-SO, respectively. Msrs are described to exert various biological functions in vivo (3-5). They can (i) repair oxidized proteins, and thus, may regulate their function, (ii) play an antioxidant role as oxidation of surface methionine residues is considered as a mechanism that scavenges reactive oxygen species without modification of the properties of proteins, and (iii) play a role in the virulence of some bacteria.The catalytic mechanism of both classes of Msrs characterized to date (6 -9) is composed of three steps including: 1) a reductase step consisting of a nucleophilic attack of the catalytic Cys residue on the sulfur atom of the sulfoxide substrate that leads to formation of a sulfenic acid intermediate and release of 1 mol of Met/mol of enzyme, 2) formation of an intradisulfide bond between the catalytic Cys and a recycling Cys with a concomitant release of 1 mol of water, and 3) reduction of the Msr disulfide bond by thioredoxin (Trx) that leads to regeneration of the reduced form of Msr and to formation of oxidized Trx. The catalytic mechanism is in agreement with the kinetic mechanism, which was shown to be of ping-pong type for both classes of Msrs (9, 10). Moreover, for both classes of Msrs, the overall rate-limiting step is associated with the Trxrecycling process, whereas the rate of formation of the intradisulfide bond is governed by that of the reductase step, the rate of which is fast (11,12).A theoretical study of the reduction mechanism of sulfoxides by thiols has been recently investigated by quantum chemistry calculations, which supp...

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Simple Cation−π Interaction between a Phenyl Ring and a Protonated Amine Stabilizes an α-Helix in Water

Cited by 100 publications

References 40 publications

Effects of Chain Length and N‐Methylation on a Cation–π Interaction in a β‐Hairpin Peptide

Effects of Chain Length and N‐Methylation on a Cation–π Interaction in a β‐Hairpin Peptide

Cross-linking Phosphatidylinositol-specific Phospholipase C Traps Two Activating Phosphatidylcholine Molecules on the Enzyme

Characterization of the Amino Acids Involved in Substrate Specificity of Methionine Sulfoxide Reductase A

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