Proton nuclear magnetic resonance study of an active pentapeptide fragment of ubiquitin

Nr, Krishna; Dh, Huang; Jb, Vaughn; Ga, Heavner; Goldstein, Gideon

doi:10.1021/bi00516a041

Cited by 8 publications

(1 citation statement)

References 50 publications

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“…constants by using poly(DL-Ala) data for k0. The examples included the acyclic cases of H-Tyr-Asn-Ile-Gln-Lys-OH ( a fragment of ubiquitin)(Krishna et al, 1981), angiotensinII (Lenkinski et al, 1981a), [Sar1 *3,Ala8]angiotensin II,…”

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confidence: 99%

Amide proton exchange rates in a cyclic dodecapeptide of defined conformation. pH and conformation dependence

Narutis¹,

Kopple²

1983

Biochemistry

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Peptide proton and side chain carboxamide proton exchange rates of the cyclic dodecapeptide cyclo-(Met-ValGly-Pro-Asn-Gly)z were determined over the pH range 1.2-9 by NMR methods. The rate constants of the base-catalyzed exchange reactions range from 2.5 to 0.006 times those predicted from measurements on N-acetyl "-methylamides of the corresponding residues, and the factors for each residue are consistent with the proposed conformation of the cyclic R o t o n exchange rates of peptide bonds have for some years been a valued tool for exploring protein conformation, since they are affected by solvent accessibility, as modulated by conformational flexibility, and by the stability of intramolecular hydrogen bonds (Hvidt & Nielsen, 1960;Englander et al., 1972;Englander, 1975;Woodward & Hilton, 1979). They have also been used, less extensively, to study conformational questions in smaller peptides. In contrast to proteins, the peptides that have been studied are not large enough to bury all aspects of a CONH unit, and most of them have considerable backbone flexibility. There are accurate kinetic data for small peptide model systems from which questions about the mechanism of exchange processes are answered for sterically unhindered systems (Molday et al., 1973), but there is not much information about conformation-induced steric influences on the elementary steps, since few oligopeptides of known conformation have been studied in a detailed way. Although cyclic peptides of sufficient complexity and conformational stability can be used to provide information about peptide bonds in a variety of defined steric situations, a review of the literature indicates that only for the cyclic decapeptide gramicidin S (Philson & Bothner-By, 1979;Krauss & Chan, 1982) are there measurements that provide good rate constants for the acid-and base-catalyzed exchange reaction of backbone protons. We considered that studies of an additional conformationally stable cyclic peptide of different backbone folding could materially add to understanding the mechanism of exchange and the influence of conformationally related steric effects on exchange.We therefore made detailed kinetic studies of proton exchange in cyclo-(Met-Val-Gly-Pro-Asn-Gly)z. NMR studies of this peptide suggest that it has a stable backbone conformation (Kopple & Go, 1977): The ranges of the NMR observables, such as coupling constants, chemical shifts, and evidence of solvent exposures, are large, indicating that conformational averaging is inhibited. The values themselves are consistent with the same backbone folding in water, methanol, dimethyl sulfoxide, and hexafluoro-2-propanol solutions, indicating that the dominant conformation is intrinsically stable.

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Amide proton exchange rates in a cyclic dodecapeptide of defined conformation. pH and conformation dependence

Narutis¹,

Kopple²

1983

Biochemistry

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Lanthanide Complexes of Peptides and Proteins

Lenkinski

1984

Biological Magnetic Resonance

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Hydrogen exchange and the dynamic structure of proteins

1982

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In native proteins, buried, labile protons undergo isotope exchange with solvent hydrogens, but the kinetics of exchange are markedly slower than in unfolded polypeptides. This indicates that, whereas buried protein atoms are shielded from solvent, the protein fluctuates around the time average structure and occasionally exposes buried sites to solvent. Generally, hydrogen exchange studies are designed to characterize the nature of the fluctuations between conformational substates, to monitor the shift in conformational equilibria among protein substates due to ligand binding or other factors, or to monitor the major cooperative denaturation transition. In this article, we review the recent reports of hydrogen exchange in proteins, focusing on recent advances in methodology, especially with regard to the implications of the results for the mechanism of hydrogen exchange in folded proteins.

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Proton nuclear magnetic resonance study of an active pentapeptide fragment of ubiquitin

Cited by 8 publications

References 50 publications

Amide proton exchange rates in a cyclic dodecapeptide of defined conformation. pH and conformation dependence

Amide proton exchange rates in a cyclic dodecapeptide of defined conformation. pH and conformation dependence

Lanthanide Complexes of Peptides and Proteins

Hydrogen exchange and the dynamic structure of proteins

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