@article {681,
	title = {Conformations of gas-phase lysozyme ions produced from two different solution conformations},
	journal = {Analytical Chemistry},
	volume = {75},
	number = {6},
	year = {2003},
	note = {ISI Document Delivery No.: 657PQTimes Cited: 15Cited Reference Count: 41},
	month = {Mar},
	pages = {1325-1330},
	type = {Article},
	abstract = {Near pH 2.0, lysozyme in water is in its native conformation, and in water/methanol (2/8) it adopts a helical denatured conformation (Kamatari et al. Protein Sci. 1998, 7, 681-688). Hydrogen/deuterium (H/D) exchange of lysozyme in solution confirms that it is partially unfolded at pH 2.0 in water/methanol (v/v = 2/8). With electrospray ionization (ESI) mass spectrometry (MS), lysozyme in water produces ions with charges +7 to +12, with the greatest intensity at +10, whereas lysozyme in water/methanol (2/8) produces ions with charges +6 to +12 with the greatest intensity at +7. Thus, lysozyme is an exception to the rule that a protein denatured in solution forms higher charge states than the same protein in its folded native conformations in solution. Because the same charge states are produced from these two solution conformations, a direct comparison of the properties of the gas-phase ions produced from two very different solution conformations is possible. The conformations of lysozyme ions in the gas phase were studied using cross section measurements and gas-phase H/D exchange. Similar cross sections and H/D exchange levels were observed for same-charge states of lysozyme ions formed from the native and helical denatured conformations in solution. Cross sections show that the ions have compact structures. Thus, disulfide-intact gaseous lysozyme ions generated from the denatured state in water/methanol (2/8) refold into compact structures in the gas phase on a time scale of milliseconds or less.},
	keywords = {COLLISION, CROSS-SECTIONS, CYTOCHROME-C, EGG-WHITE LYSOZYME, H/D EXCHANGE, HYDROGEN-DEUTERIUM EXCHANGE, HYDROGEN/DEUTERIUM EXCHANGE, IONIZATION MASS-SPECTROMETRY, IONS, OF-FLIGHT SYSTEM, PROTEIN, UNFOLDING DYNAMICS},
	isbn = {0003-2700},
	url = {<Go to ISI>://000181675900014},
	author = {Mao, D. M. and Babu, K. R. and Chen, Y. L. and Douglas, D. J.}
}
@article {682,
	title = {H/D exchange of gas phase bradykinin ions in a linear quadrupole ion trap},
	journal = {Journal of the American Society for Mass Spectrometry},
	volume = {14},
	number = {2},
	year = {2003},
	note = {ISI Document Delivery No.: 643ZYTimes Cited: 14Cited Reference Count: 51},
	month = {Feb},
	pages = {85-94},
	type = {Article},
	abstract = {The gas phase H/D exchange reaction of bradykinin ions, as well as fragment ions of bradykinin generated through collisions in an orifice skimmer region, have been studied with a linear quadrupole ion trap (LIT) reflectron time-of-flight (rTOF) mass spectrometer system. The reaction in the trap takes only tens of seconds at a pressure of few mTorr of D2O or CD3OD. The exchange rate and hydrogen exchange level are not sensitive to the trapping q value over a broad range, provided q is not close to the stability boundary (q = 0.908). The relative rates and hydrogen exchange levels of protonated and sodiated +1 and +2 ions are similar to those observed previously by others with a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer system. The doubly and triply protonated ions show multimodal isotopic distributions, suggesting the presence of several different conformations. The y fragment ions show greater exchange rates and levels than a or b ions, and when water or ammonia is lost from the fragment ions, no exchange is observed. (J Am Soc Mass Spectrom 2003, 14, 85-94) (C) 2003 American Society for Mass Spectrometry.},
	keywords = {ACTIVATED DISSOCIATION, COLLISIONAL ACTIVATION, CYTOCHROME-C, HYDROGEN-DEUTERIUM EXCHANGE, HYDROGEN/DEUTERIUM EXCHANGE, INFRARED, IONIZATION MASS-SPECTROMETRY, OF-FLIGHT SYSTEM, PEPTIDE IONS, PROTEIN IONS, RADIATIVE DISSOCIATION},
	isbn = {1044-0305},
	url = {<Go to ISI>://000180894500001},
	author = {Mao, D. M. and Douglas, D. J.}
}
@article {439,
	title = {Hydrogen/deuterium exchange of myoglobin ions in a linear quadrupole ion trap},
	journal = {Rapid Communications in Mass Spectrometry},
	volume = {16},
	number = {20},
	year = {2002},
	note = {ISI Document Delivery No.: 604ADTimes Cited: 10Cited Reference Count: 26},
	pages = {1941-1945},
	type = {Article},
	abstract = {The hydrogen/deuterium (H/D) exchange of gas-phase ions of holo- and apo-myoglobin has been studied by confining the ions in a linear quadrupole ion trap with D2O or CD3OD at a pressure of several mTorr. Apo-myoglobin ions were formed by collision-induced dissociation of holomyoglobin ions between the orifice and skimmer of the ion sampling system. The exchange takes place on a time scale of seconds. Earlier cross section measurements have shown that holomyoglobin ions can have more compact structures than apo-myoglobin. Despite this, both holomyoglobin and apo-myoglobin in charge states +8 to +14 are found to exchange nearly the same number of hydrogens (ca. 103) in 4 s. It is possible the ions fold or unfold to new conformations on the much longer time scale of the exchange experiment compared with the cross section measurements. Copyright (C) 2002 John Wiley Sons, Ltd.},
	keywords = {COLLISION CROSS-SECTIONS, CYTOCHROME-C, GAS-PHASE, HEME, HOLOMYOGLOBIN, HYDROGEN-DEUTERIUM EXCHANGE, MASS-SPECTROMETRY, OF-FLIGHT, PROTEIN IONS, STABILITY, SYSTEM},
	isbn = {0951-4198},
	url = {<Go to ISI>://000178592700007},
	author = {Mao, D. M. and Ding, C. F. and Douglas, D. J.}
}
@article {4314,
	title = {Equilibrium unfolding of proteins monitored by electrospray ionization mass spectrometry: Distinguishing two-state from multi-state transitions},
	journal = {Rapid Communications in Mass Spectrometry},
	volume = {12},
	number = {8},
	year = {1998},
	note = {ISI Document Delivery No.: ZJ143Times Cited: 79Cited Reference Count: 59},
	pages = {435-442},
	type = {Article},
	abstract = {The acetic acid-induced unfolding of cytochrome c (cyt c) and apomyoglobin (aMb) are studied under equilibrium conditions by electrospray ionization (ESI) mass spectrometry (MS), The folding states of the proteins in solution are monitored by the charge state distributions that they produce during ESI, A tightly folded protein shows lower charge states than the same protein in an unfolded conformation. The ESI-MS data presented in this study show that during the denaturation of cyt c, only two distinct charge state distributions are observed. These can be attributed to the native and to the acid-unfolded conformation, respectively. In the transition region where the folded and the unfolded conformation are both present in solution, these two distributions are observed simultaneously, thus giving rise to a bimodal ESI mass spectrum. These data reflect a highly cooperative (two state) folding behavior. In contrast, the acid-induced unfolding of aMb is accompanied by gradual shifts in the maxima of the observed charge state distribution. This indicates a non cooperative unfolding behavior involving multiple protein conformations. The observations made here suggest that ESI-MS might be a general method for assessing the cooperativity of protein unfolding transitions. This study also addresses the issue of {\textquoteright}secondary{\textquoteright} solvent effects for ESI-MS studies on the acid-induced unfolding of proteins. These effects influence the ESI charge state distribution without being related to conformational changes of the protein in solution and could potentially complicate the interpretation of ESI mass spectra, Data obtained for bovine pancreatic trypsin inhibitor and ubiquitin indicate that secondary solvent effects influence the observed charge state distributions only to a very minor extent between pH 8.5 and 2.5. (C) 1998 John Wiley \& Sons, Ltd.},
	keywords = {CONFORMATIONAL-CHANGES, CYTOCHROME-C, FERRICYTOCHROME-C, FOLDING, HYDROGEN-DEUTERIUM EXCHANGE, INTERMEDIATE, MOLECULAR-BASIS, MOLTEN GLOBULE, NMR-SPECTROSCOPY, POSITIVE-ION, STRUCTURAL CHARACTERIZATION},
	isbn = {0951-4198},
	url = {<Go to ISI>://000073183800005},
	author = {Konermann, L. and Douglas, D. J.}
}
@article {4313,
	title = {Unfolding of proteins monitored by electrospray ionization mass spectrometry: A comparison of positive and negative ion modes},
	journal = {Journal of the American Society for Mass Spectrometry},
	volume = {9},
	number = {12},
	year = {1998},
	note = {ISI Document Delivery No.: 141FPTimes Cited: 72Cited Reference Count: 56},
	month = {Dec},
	pages = {1248-1254},
	type = {Article},
	abstract = {Electrospray ionization (ESI) mass spectrometry (MS) in both the positive and negative ion mode has been used to study protein unfolding transitions of lysozyme, cytochrome c (cyt c), and ubiquitin in solution. As expected, ESI of unfolded lysozyme leads to the formation of substantially higher charge states than the tightly folded protein in both modes of operation. Surprisingly, the acid-induced unfolding of cyt c as well as the acid and the base-induced unfolding of ubiquitin show different behavior: In these three cases protein unfolding only leads to marginal changes in the negative ion charge state distributions, whereas in the positive ion mode pronounced shifts to higher charge states are observed. This shows that ESI MS in the negative ion mode as a method for probing conformational changes of proteins in solution should be treated with caution. The data presented in this work provide further evidence that the conformation of a protein in solution not its charge state is the predominant factor for determining the ESI charge slate distribution in the positive ion mode. Furthermore, these data support the hypothesis of a recent study (Konermann and Douglas, Biochemistry 1997, 36, 12296-12302) which suggested that ESI in the positive ion mode is not sensitive to changes in the secondary structure of proteins but only to changes in the tertiary structure. (C) 1998 American Society for Mass Spectrometry.},
	keywords = {A-STATE, BINDING, CIRCULAR-DICHROISM, CYTOCHROME-C, HYDROGEN-DEUTERIUM EXCHANGE, INDUCED CONFORMATIONAL-CHANGES, MYOGLOBIN, NUCLEAR-MAGNETIC-RESONANCE, SITES, SPECTRA, UBIQUITIN},
	isbn = {1044-0305},
	url = {<Go to ISI>://000077132600002},
	author = {Konermann, L. and Douglas, D. J.}
}
@article {3799,
	title = {Characterization of a buried neutral histidine residue in Bacillus circulans xylanase: NMR assignments, pH titration, and hydrogen exchange},
	journal = {Protein Science},
	volume = {5},
	number = {11},
	year = {1996},
	note = {ISI Document Delivery No.: VQ786Times Cited: 41Cited Reference Count: 63},
	month = {Nov},
	pages = {2319-2328},
	type = {Article},
	abstract = {Bacillus circulans xylanase contains two histidines, one of which (His 156) is solvent exposed, whereas the other (His 149) is buried within its hydrophobic core. His 149 is involved in a network of hydrogen bonds with an internal water and Ser 130, as well as a potential weak aromatic-aromatic interaction with Tyr 105. These three residues, and their network of interactions with the bound water, are conserved in four homologous xylanases. To probe the structural role played by His 149, NMR spectroscopy was used to characterize the histidines in BCX. Complete assignments of the H-1, C-13, and N-15 resonances and tautomeric forms of the imidazole rings were obtained from two-dimensional heteronuclear correlation experiments. An unusual spectroscopic feature of BCX is a peak near 12 ppm arising from the nitrogen bonded H-1(epsilon 2) of His 149. Due to its solvent inaccessibility and hydrogen bonding to an internal water molecule, the exchange rate of this proton (4.0 X 10(-5) s(-1) at pH* 7.04 and 30 degrees C) is retarded by > 10(6)-fold relative to an exposed histidine. The pK(a) of His 156 is unperturbed at similar to 6.5, as measured from the pH dependence of the N-15- and H-1-NMR spectra of BCX. In contrast, His 149 has a pK(a) < 2.3, existing in the neutral (NH)-H-epsilon 2 tautomeric state under all conditions examined. BCX unfolds at low pH and 30 degrees C, and thus His 149 is never protonated significantly in the context of the native enzyme. The structural importance of this buried histidine is confirmed by the destablizing effect of substituting a phenylalanine or glutamine at position 149 in BCX.},
	keywords = {ACTIVE-SITE, ALPHA-HELICES, AQUEOUS-SOLUTION, CHEMICAL-SHIFTS, ESCHERICHIA-COLI, GLYCOSYL HYDROLASES, H-1-NMR SPECTRUM, HYDROGEN-DEUTERIUM EXCHANGE, IMIDAZOLE, internal water, L-ALA-OH, NUCLEAR MAGNETIC-RESONANCE, pH titration, pK(alpha), PROTEIN HYDRATION, protein stability},
	isbn = {0961-8368},
	url = {<Go to ISI>://A1996VQ78600018},
	author = {Plesniak, L. A. and Connelly, G. P. and Wakarchuk, W. W. and McIntosh, L. P.}
}
