The rate of exchange of peptide group NH hydrogens with the hydrogens of aqueous solvent is sensitive to neighboring side chains. To evaluate the effects of protein side chains, all 20 naturally occurring amino acids were studied using dipeptide models. Both inductive and steric blocking effects are apparent. The additivity of nearest-neighbor blocking and inductive effects was tested in oligo- and polypeptides and, surprisingly, confirmed. Reference rates for alanine-containing peptides were determined and effects of temperature considered. These results provide the information necessary to evaluate measured protein NH to ND exchange rates by comparing them with rates to be expected for the same amino acid sequence is unstructured oligo- and polypeptides. The application of this approach to protein studies is discussed.

Primary Structure Effects on Peptide Group Hydrogen Exchange

Though the structures presented in crystallographic models of macromolecules appear to possess rock-like solidity, real proteins and nucleic acids are not particularly rigid. Most structural work to date has centred upon the native state of macromolecules, the most probable macromolecular form. But the native state of a molecule is merely its most abundant form, certainly not its only form. Thermodynamics requires that all other possible structural forms, however improbable, must also exist, albeit with representation corresponding to the factor exp( — Gi/RT) for each state of free energy Gi (see Moelwyn-Hughes, 1961), and one appreciates that each molecule within a population of molecules will in time explore the vast ensemble of possible structural states.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033583500005217

Hydrogen exchange and structural dynamics of proteins and nucleic acids

Publisher Summary The chapter reviews the results obtained from measurements of hydrogen exchange (H–H, H–D, and H–T) in proteins and related compounds. The slowness of the rate of hydrogen exchange in a protein, relative to the exchange rate observed with simple peptides under the same experimental conditions is closely related to the conformation of the protein molecule in aqueous solution. Quantitative measurements of the rate of hydrogen exchange in a given protein, under specified experimental conditions, provide a multiparameter characterization of the protein conformation (or distribution of conformations) present under these conditions. Moreover, the chapter discusses the experimental techniques that have been used to measure quantitatively the rate of hydrogen exchange. The chapter also discusses arguments that support case, as the mechanism of exchange of the slowly exchanging hydrogen atoms.

Hydrogen exchange in proteins.

Primary structure effects on peptide group hydrogen exchange.

Das Proton nimmt als Trager und Vermittler chemischer Reaktionen in der Losungsphase eine ausgezeichnete Stellung ein. Viele Reaktionen der organischen Chemie werden durch Sauren oder Basen katalysiert; insbesondere aber enthalten die meisten Enzyme Wirkgruppen, die eine Saure-Base-Katalyse vermitteln. Ein Verstandnis der Reaktionsmechanismen setzt die Kenntnis der Elementarschritte und ihres zeitlichen Ablaufs voraus. Die systematische Untersuchung dieser Elementarschritte ist erst durch die Entwicklung neuer Methoden zur Untersuchung sehr schneller Reaktionen moglich geworden. In der vorliegenden Arbeit wird zusammenfassend uber die Ergebnisse derartiger Untersuchungen berichtet. Sie ergeben ein relativ vollstandiges Bild der Elementarmechanismen der Protonenubertragung und fuhren zu einer umfassenden Beschreibung der Gesetzmasigkeiten der Saure-Base- und Enzym-Katalyse.

A. Berger

Papers

Nuclear Magnetic Resonance Study of the Protolysis and Ionization of N-Methylacetamide1