Dissociation Behavior of Doubly-Charged Tryptic Peptides:  Correlation of Gas-Phase Cleavage Abundance with Ramachandran Plots

Huang, Yingying; Triscari, Joseph; Paša‐Tolić, Ljiljana; Anderson, Gordon A.; Lipton, Mary; Smith, Richard D.; Wysocki, Vicki H.

doi:10.1021/ja038041t

Cited by 68 publications

(117 citation statements)

References 20 publications

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“…This unique fragmentation is contradictory to trends previously established by statistical analysis of peptide tandem mass (MS/MS) spectra [1][2][3][4]. Substitution of alanine for aspartic acid (i.e., VPAPR) did not change the fragmentation, indicating the cleavage was not directed by aspartic acid.…”

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confidence: 79%

“…Attempts to understand the limitations of these algorithms and improve the fragmentation model are being made. Some recent strategies involve statistical analysis of fragmentation patterns of peptide MS/MS spectra [1][2][3][4]22] and studying the chemistry involved in peptide fragmentation mechanisms [23][24][25][26][27][28][29][30][31][32] to more intelligently predict …”

mentioning

confidence: 99%

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Investigation of gas phase ion structure for proline-containing b₂ ion

Smith

Herrmann

Wysocki

2006

J. Am. Soc. Mass Spectrom.

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Unusual fragmentation was observed for doubly charged VPDPR in which cleavage Cterminal to proline and N-terminal to aspartic acid yielded b 2 (ϩ a 2 )/y 3 complementary ions. This unique fragmentation is contradictory to trends previously established by statistical analysis of peptide tandem mass (MS/MS) spectra [1][2][3][4]. Substitution of alanine for aspartic acid (i.e., VPAPR) did not change the fragmentation, indicating the cleavage was not directed by aspartic acid. Fragmentation patterns for VPAPR and V(NmA)APR (NmA ϭ N-methyl alanine) were compared to determine whether conformational constraints from proline's cyclic side-chain contribute to b 2 ion formation. While both peptide sequences fragmented to yield b 2 /y 3 ions, only VPAPR produced a 2 ions, suggesting the VP b 2 ion is structurally different from the V(NmA) b 2 ion. Instead, the V(NmA) b 2 ion was accompanied by an ion corresponding to formal loss of 71. The suspected structural differences were confirmed by isolation and fragmentation of the respective b 2 ions (i.e., MS 3 spectra). Evidence supporting a diketopiperazine structure for the VP b 2 ion is reported. Fragmentation patterns for the VP b 2 ion and a synthetic VP diketopiperazine showed great similarity. N-terminal acetylation of VPAPR prevented the formation of the VP b 2 ion, presumably by blocking nucleophilic attack by the N-terminal amine on the carbonyl oxygen of the protonation site. Acetylation of the N-terminus for V(NmA)APR did not prevent the formation of the V(NmA) b 2 ion, indicating the V(NmA) b 2 ion has a structure, presumably that of an oxazolone, which requires no attack by the N-terminus for formation. Finally, high-resolution, accurate mass measurements M ass spectrometry is playing a key role, in conjunction with other analytical tools (e.g., electrophoretic and multidimensional separations and sequence database searching algorithms), to elucidate gene function from protein expression profiles [5][6][7][8][9]. Peptide sequence information is obtained by using tandem mass spectrometry (MS/MS) and lowenergy collision induced dissociation (CID) to identify individual proteins. Useful algorithms like SEQUEST [10] and Mascot [11] have been developed to identify proteins by matching raw MS/MS CID spectra with peptide sequences from protein or translated nucleotide sequence databases. The predictive model of peptide fragmentation used by most current automated peptide sequencing algorithms anticipates cleavage of all amide bonds along the peptide backbone, presumably resulting in the formation of b n and y n ions, using Roepstorff/ Biemann nomenclature [12,13]. Other ion types are also formed that can be useful in automated peptide sequencing, including a n ions, immonium ions, internal sequence ions, and neutral losses of ammonia and water from these ions. Differences between the m/z values of adjacent fragment ions of the same series can be correlated to the mass of an amino acid residue. Thus, a complete series of either of these ion types allows the sequencing of ...

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confidence: 99%

Investigation of gas phase ion structure for proline-containing b₂ ion

Smith

Herrmann

Wysocki

2006

J. Am. Soc. Mass Spectrom.

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“…The former leads to generation of isobaric, but differentially modified, peptides that often co-elute, producing chimeric spectra difficult to interpret without the aid of high mass accuracy and abundant product ions from MS n . The latter hampers MS n sequencing efforts due the propensity of Pro/Hyp to preferentially cleave during collisional activation (the "proline effect") (33,34). This can limit the generation of a ladder of b-and y-type product ions most commonly used by database search algorithms for peptide identification and PTM localization of spectra generated by collision-activated dissociation (33,(35)(36)(37).…”

Section: Collagen Type V (Col(v))mentioning

confidence: 99%

Comprehensive Mass Spectrometric Mapping of the Hydroxylated Amino Acid residues of the α1(V) Collagen Chain

Yang

Park

Davis

et al. 2012

Journal of Biological Chemistry

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Background: ␣1(V) is an extensively modified collagen chain important in disease. Results: Comprehensive mapping of ␣1(V) post-translational modifications reveals unexpectedly large numbers of X-position hydroxyprolines in Gly-X-Y amino acid triplets. Conclusion:The unexpected abundance of X-position hydroxyprolines suggests a mechanism for differential modification of collagen properties. Significance: Positions, numbers, and occupancy of modified sites can provide insights into ␣1(V) biological properties.

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“…Since that time, improvements in sequencing have been spurred by the development of protein-identification algorithms as well as a better understanding of peptide dissociation in the gas phase. The latter advancement has been achieved by exploring the effects of peptide size, sequence, gasphase basicity, charge state, and secondary structure on fragmentation [62][63][64][65][66][67][68][69][70]. Surface-induced dissociation was influential in helping to develop a general framework for peptide fragmentation through the energyresolved study of systematically varied model peptides.…”

Section: The Role Of Sid In Developing the Mobile Proton Model And Elmentioning

confidence: 99%

Surface-induced dissociation of small molecules, peptides, and non-covalent protein complexes

Wysocki

Joyce

Jones

et al. 2008

J. Am. Soc. Mass Spectrom.

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This article provides a perspective on collisions of ions with surfaces, including surfaceinduced dissociation (SID) and reactive ion scattering spectrometry (RISS). The content is organized into sections on surface-induced dissociation of small ions, surface characterization of organic thin films by collision of well-characterized ions into surfaces, the use of SID to probe peptide fragmentation, and the dissociation of large non-covalent complexes by SID. Examples are given from the literature with a focus on experiments from the authors' laboratory. The article is not a comprehensive review but is designed to provide the reader with an overview of the types of results possible by collisions of ions into surfaces. (J Am Soc Mass Spectrom 2008, 19, 190 -208) © 2008 American Society for Mass Spectrometry T andem mass spectrometry (MS/MS) is an essential tool for elucidating ion structure. The MS/MS experiment involves mass selection of a precursor ion followed by ion activation and subsequent dissociation. The ion activation step is commonly accomplished via collision-induced dissociation (CID) in which the initial kinetic energy of a projectile ion is converted into internal energy through inelastic collisions with a neutral gas. Several alternative activation methods have been used in tandem mass spectrometry, one of which is surfaceinduced dissociation (SID). SID is analogous to CID, except that a surface replaces the neutral gas as the collision target. A typical ion-surface collision event is illustrated in Figure 1.The incorporation of a surface into a mass spectrometer for ion activation was pioneered in the laboratory of R. Graham Cooks in the mid-1970s and early 1980s [1][2][3]. Since that time, collisions of lowenergy (eV) organic ions with surfaces within the tandem mass spectrometer have been valuable for analyzing surface composition, characterizing reactions between organic projectile ions and surface adsorbates, chemically modifying surfaces, and determining projectile ion structure. A major motivation for development of SID is that energy transfer to ionic projectiles can be improved by increasing the mass of the collision target. The total available energy for transfer into the internal modes of the projectile ion is defined by the center-of-mass energy (E COM ) described by eq 1:where E LAB is the laboratory collision energy and M ION and M N are the masses of the projectile ion and neutral, respectively. Energy transfer in CID is limited by the mass of the collision partner, typically inert gases such as helium, argon, or xenon. In SID, if one assumes that the surface is an infinitely large collision partner, E COM becomes independent of mass and approaches the laboratory collision energy. The assumption that the entire surface can be viewed as the collision partner is not always valid, however, and there are instances where the mass of the terminal groups on the surface influence the amount of energy transfer [4,5]. Nonetheless, the use of a massive surface target should, in theory, provide ...

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Dissociation Behavior of Doubly-Charged Tryptic Peptides: Correlation of Gas-Phase Cleavage Abundance with Ramachandran Plots

Cited by 68 publications

References 20 publications

Investigation of gas phase ion structure for proline-containing b₂ ion

Investigation of gas phase ion structure for proline-containing b₂ ion

Comprehensive Mass Spectrometric Mapping of the Hydroxylated Amino Acid residues of the α1(V) Collagen Chain

Surface-induced dissociation of small molecules, peptides, and non-covalent protein complexes

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Dissociation Behavior of Doubly-Charged Tryptic Peptides: Correlation of Gas-Phase Cleavage Abundance with Ramachandran Plots

Cited by 68 publications

References 20 publications

Investigation of gas phase ion structure for proline-containing b2 ion

Investigation of gas phase ion structure for proline-containing b2 ion

Comprehensive Mass Spectrometric Mapping of the Hydroxylated Amino Acid residues of the α1(V) Collagen Chain

Surface-induced dissociation of small molecules, peptides, and non-covalent protein complexes

Contact Info

Product

Resources

About

Investigation of gas phase ion structure for proline-containing b₂ ion

Investigation of gas phase ion structure for proline-containing b₂ ion