Dataset Information

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS) and Tyr(CysS): a computational study.

ABSTRACT: Density Functional Theory (DFT) calculations were carried out to evaluate the potential for intramolecular addition of peptide cysteine (Cys) thiyl radicals (CysS(*)) to aromatic amino acids (Phe and Tyr) in water. These calculations yielded cyclic conformations, in which pi-complexes were more stable than cyclohexadienyl radicals in water. In these pi-complexes, the C(2)-S distances were significantly shorter compared to the C(1)-S and C(3)-S distances. Comparable results on the relative stabilities were obtained for model calculations for the addition of HS(*)/CH(3)S(*) to toluene and p-hydroxytoluene. The adduct of thiyl radicals with Phe was more stable than that with Tyr, and the stabilization energies depended on the C-terminal substituents.

SUBMITTER: Naumov S

PROVIDER: S-EPMC2774831 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS) and Tyr(CysS): a computational study.

Naumov Sergej S Schöneich Christian C

The journal of physical chemistry. A 20090401 15

Density Functional Theory (DFT) calculations were carried out to evaluate the potential for intramolecular addition of peptide cysteine (Cys) thiyl radicals (CysS(*)) to aromatic amino acids (Phe and Tyr) in water. These calculations yielded cyclic conformations, in which pi-complexes were more stable than cyclohexadienyl radicals in water. In these pi-complexes, the C(2)-S distances were significantly shorter compared to the C(1)-S and C(3)-S distances. Comparable results on the relative stabil ...[more]

PMID: 19309133

Similar Datasets

Project description:Aromatic amino acids often flank the transmembrane alpha helices of integral membrane proteins. By favoring locations within the membrane-water interface of the lipid bilayer, aromatic residues Trp, Tyr, and sometimes Phe may serve as anchors to help stabilize a transmembrane orientation. In this work, we compare the influence of interfacial Trp, Tyr, or Phe residues upon the properties of tilted helical transmembrane peptides. For such comparisons, it has been critical to start with no more than one interfacial aromatic residue near each end of a transmembrane helix, for example, that of GWALP23 (acetyl-GGALW(5)(LA)6LW(19)LAGA-[ethanol]amide). To this end, we have employed (2)H-labeled alanines and solid-state NMR spectroscopy to investigate the consequences of moving or replacing W5 or W19 in GWALP23 with selected Tyr, Phe, or Trp residues at the same or proximate locations. We find that GWALP23 peptides having F5, Y5, or W5 exhibit essentially the same average tilt and similar dynamics in bilayer membranes of 1,2-dilauroylphosphatidylcholine (DLPC) or 1,2-dioleoylphosphatidylcholine (DOPC). When double Tyr anchors are present, in Y(4,5)GWALP23 the NMR observables are markedly more subject to dynamic averaging and at the same time are less responsive to the bilayer thickness. Decreased dynamics are nevertheless observed when ring hydrogen bonding is removed, such that F(4,5)GWALP23 exhibits a similar extent of low dynamic averaging as GWALP23 itself. When F5 is the sole aromatic group in the N-interfacial region, the dynamic averaging is (only) slightly more extensive than with W5, Y5, or Y4 alone or with F4,5, yet it is much less than that observed for Y(4,5)GWALP23. Interestingly, moving Y5 to Y4 or W19 to W18, while retaining only one hydrogen-bond-capable aromatic ring at each interface, maintains the low level of dynamic averaging but alters the helix azimuthal rotation. The rotation change is about 40° for Y4 regardless of whether the host lipid bilayer is DLPC or DOPC. The rotational change (??) is more dramatic and more complex when W19 is moved to W18, as ?? is about +90° in DLPC but about -60° in DOPC. Possible reasons for this curious lipid-dependent helix rotation could include not only the separation distances between flanking aromatic or hydrophobic residues but also the absolute location of the W19 indole ring. For the more usual cases, when the helix azimuthal rotation shows little dependence on the host bilayer identity, excepting W(18)GWALP23, the transmembrane helices adapt to different lipids primarily by changing the magnitude of their tilt. We conclude that, in the absence of other functional groups, interfacial aromatic residues determine the preferred orientations and dynamics of membrane-spanning peptides. The results furthermore suggest possibilities for rotational and dynamic control of membrane protein function.

Dataset Information

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS) and Tyr(CysS): a computational study.

Publications

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS) and Tyr(CysS): a computational study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS*) and Tyr(CysS*): a computational study.

Publications

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS*) and Tyr(CysS*): a computational study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS) and Tyr(CysS): a computational study.

Intramolecular addition of cysteine thiyl radical to phenylalanine and tyrosine in model peptides, Phe (CysS) and Tyr(CysS): a computational study.