Hydrogen–deuterium exchange of the C-2 protons of histidine and histidine peptides and proteins

Bradbury, J. H.; Chapman, Bogdan E.; Crompton, Malcolm W.; Norton, Raymond S.; Teh, Joo Seng

doi:10.1039/p29800000693

Cited by 20 publications

(23 citation statements)

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“…The HX reaction has been shown to follow pseudo-first-order kinetics, in which the abstraction of the C ε1 -proton from the cationic imidazolium by OD − to form a ylide or a carbene intermediate is the rate-determining step (2–4). The rate profile of the HX reaction as a function of pD yields a sigmoidal curve, which exhibits a progression from the acidic side that accelerates and approaches the plateau on the alkaline side of the sigmoidal curve (Figure 1) (2–6). The rate profile provides two useful parameters that indicate the local environment of the given imidazole group in a protein.…”

Section: Introductionmentioning

confidence: 99%

“…However, the relationship between the HX rate and solvent accessibility is not straightforward. According to the kinetic studies of the HX reaction (2–4, 6), the reaction rate is expressed by Equation 1:

rate = k [{Im}_{total}] = k_{2} [{Im}^{+}] [{OD}^{-}]

where k is the pseudo first-order rate constant; k 2 is the second order rate constant for the rate-determining step of the HX reaction; [Im total ] and [Im + ] represent the concentrations of total imidazole and the charged form of imidazole, respectively; and [OD − ] is the concentration of deuteroxyl ions. Because…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Measurement of the Solvent Accessibility of Histidine Imidazole Groups in Proteins

et al. 2012

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We report a method to express the solvent accessibility of histidine imidazole groups in proteins. The method is based on measuring the rate of hydrogen exchange (HX) reaction of the imidazole Cε1-hydrogen. The rate profile of the HX reaction as a function of pH gives a sigmoidal curve, which reaches the maximum rate constant (kmax) on the alkaline side of the sigmoidal curve. To quantitatively describe the solvent accessibility of imidazole groups in proteins, it is necessary to compare the kmax of the imidazole groups with their intrinsic kmax (ikmax), the maximum rate constants for the given imidazole groups when they are fully exposed to the bulk solvent. However, the mechanism of HX reaction suggests that the ikmax of an imidazole group differs depending on its pKa, and no systematic study has been conducted to clarify how the ikmax is affected by pKa. We therefore investigated the relationship between ikmax and pKa using four imidazole derivatives at three different temperatures. The experimentally determined pKa-specific ikmax values allowed us to derive a general formula to estimate the ikmax value of any given imidazole group exhibiting a specific pKa at a specific temperature. Using the formula, the protection factors (PF), the ratio of ikmax to kmax, of five imidazole groups in dihydrofolate reductase were obtained and used to express the magnitude of their solvent accessibility. In this definition, the smaller the PF value, the higher the solvent accessibility, and a value of 1 indicates full exposure to the bulk solvent. The solvent accessibility expressed by the PF values agreed well with the solvent accessible surface areas (ASA) obtained from the X-ray diffraction data.

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Section: Introductionmentioning

confidence: 99%

rate = k [{Im}_{total}] = k_{2} [{Im}^{+}] [{OD}^{-}]

Section: Introductionmentioning

confidence: 99%

Quantitative Measurement of the Solvent Accessibility of Histidine Imidazole Groups in Proteins

et al. 2012

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“…The absence of a similar resonance shift of the B5 histidine resonances of molecule 2 may be due to a balancing of a downfield shift due to tetrahedral Zn binding, with an upfield ring current shift due to a neighbouring B10 histidine of molecule 2 (15). The assignment of resonances 1 and 2 in the 4 Z n form to H-2 histidine resonances has been confirmed by removal of the resonances by 'H-'H exchange in a separate exchange experiment (15,19). Resonance peak 8 at 6.919 p.p.m.…”

Section: Addition Of Thiocyanate To 2 Zn Insulinmentioning

confidence: 84%

1H n.m.r. studies of insulin

Ramesh¹,

Bradbury²

1986

International Journal of Peptide and Protein Research

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1H n.m.r. studies at 270 MHz were made of the transformation of 2 Zn insulin hexamer to 4 Zn hexamer produced by the addition of anions (thiocyanate ion). Four separate H2 histidine resonances were observed for the B5 and B10 histidines in 2 Zn hexamer at pH 7 and 9 and four separate resonances also occurred in the 4 Zn hexamer. The observation of these resonances and others from phenylalanine, tyrosine and leucine residues showed that the 2 Zn to 4 Zn transformation probably occurred in solution in a similar manner to that observed in the crystal. Furthermore as occurred in the crystal, it was found that in solution the transformation was reversible (on removal of thiocyanate) and that 2 Cd insulin was unable to undergo the transformation. Des‐Phe‐B1‐insulin did not undergo the transformation. Addition of SCN˜ to Zn‐free insulin (mainly dimer) produced only a small transformation, consistent with the idea that Zn2 + promotes formation of hexamer from dimer but probably does not otherwise affect the transformation.

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“…These factors have different bearing on the isotopic exchange process of the imidazole C-2 proton ; hydrophobic screening lowers the isotopic exchange rate constants (k, and kb), whereas positively charged groups increase the kb value [35,39]. From Table 3 it can be seen that such an increase occurs with His-4, His-32 and His-53 imidazole rings leading to the inference of their closeness to positively charged amino and/or guanidine groups.…”

Section: Histidine Residuesmentioning

confidence: 89%

“…The constant k, can be lower than the usual value (4 x s-l M-' at 40°C for N-acetylhistidine [34]) when the imidazole ring is buried in the protein globule or equal to this value when the imidazole ring is solvent exposed [35]. The kb rate constants are lower than normal for the imidazole ring buried in the protein globule or when it is near to negatively charged groups and is higher than normal if the imidazole ring is in the vicinity of positively charged groups [35].…”

Section: Histidine Residuesmentioning

confidence: 99%

The 1H Nuclear-Magnetic-Resonance Spectra and Spatial Structure of the Naja mossambica mossambica Neurotoxin III

Arseniev¹,

Pashkov²,

Pluzhnikov³

et al. 1981

Eur J Biochem

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The proton NMR spectra at 300 MHz of neurotoxin 111 from venom of Naju mossumbicu mossamhicu are reported. By the use of double resonance techniques, pH dependence chemical shifts, isotope labeling technique, and comparison with homologous neurotoxins all proton signals in the aromatic and methyl regions as well as E -C H~ proton signals of some lysine residues have been assigned to individual amino acid residues and their spatial microenvironment has been determined. The results deduced on the solution structure of neurotoxin I11 are in complete agreement with the crystal structure of sea snake erabutoxins as well as with the previously established backbone folding and inter-residue interactions for the Naju naja oxiana short-chain neurotoxin in solution. In addition evidence has been obtained (a) that the conformation of the p turn in the 31 -34 segment depends on the ionization state of the Asp-31 and His-32 side chain groups and (b) that an intricate electrostatic interaction exists in a system of ionogenic groups of the invariant Lys-27, Lys-47, Asp-31, Arg-33, Glu-38 and His-32 residues. These aspects of dynamic conformation are related to an interaction mechanism of a neurotoxin molecule and a nicotinic acetylcholine receptor.Polypeptide toxins are useful probes for studying neuroconductivity processes on the molecular level. Particular attention is being allotted to toxins of sea and amphibious snakes, blocking transmission of the nerve impulse by specifically binding to the acetylcholine receptor of the postsynaptic membrane [I -31.At present the amino acid sequence of about 30 so-called short-chain neurotoxins (60 -62 amino acid residues with four disulphide bonds) from snake venoms has been determined [4]. A crystal structure is determined for two members of this neurotoxin group, erabutoxin a and b of Laticaudu semifasciala [5,6]. The solution conformation of short-chain neurotoxins is being intensively investigated by various physicochemical methods [7-91. Of these the most informative has proved to be NMR spectroscopy in combination with selective chemical modification [lo-221 so as to insert reporter groups into given sites of the protein molecule. Such an approach has made possible determination of the solution conformation of the central loop (residues 23 -38) of the Naja nu@ oxiana neurotoxin I1 [14-181.The absence of suitable reporter groups for the other parts of the molecule and the difficulty of inserting such groups in these parts had been a stumbling block to their NMR conformational characterization. However, molecules with natural reporter groups in the segments of interest could be selected from the extensive homologous series of the 'short' neurotoxin molecules. In particular several such convenient reporter natural ainino acid residues are to be found in the pertinent segments of the Nuju mossambica mossambica neurotoxin I11 molecule (Fig. 1) which we have studied.Of course, making use of the data obtained from the other members of the homologous neurotoxins is possible under the pro...

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Hydrogen–deuterium exchange of the C-2 protons of histidine and histidine peptides and proteins

Cited by 20 publications

References 1 publication

Quantitative Measurement of the Solvent Accessibility of Histidine Imidazole Groups in Proteins

Quantitative Measurement of the Solvent Accessibility of Histidine Imidazole Groups in Proteins

1H n.m.r. studies of insulin

The 1H Nuclear-Magnetic-Resonance Spectra and Spatial Structure of the Naja mossambica mossambica Neurotoxin III

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