Aspartylglycosaminuria in the Finnish population: identification of two point mutations in the heavy chain of glycoasparaginase.

Mononen, Ilkka; Heisterkamp, Nora; Kaartinen, Vesa; Williams, Julian C.; Yates, John R.; Griffin, Patrick R.; Hood, Leroy; Groffen, John

doi:10.1073/pnas.88.7.2941

Cited by 46 publications

(24 citation statements)

References 14 publications

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“…Although these peptides were produced by a chymotrypsin digest of the protein, this information was not included in the computer analysis. In this process 50% of the sequence was confirmed against the nucleotide-derived protein sequence with less than 1 min of data analysis time [35]. By combining this data analysis approach with automated LC-MS/MS techniques [36], highly specific amino acid sequence information can be obtained and analyzed concurrent with the analysis.…”

Section: Application Of the Search Program To Singlementioning

confidence: 99%

An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database

Eng

McCormack

Yates

1994

J. Am. Soc. Mass Spectrom.

6,258

5,480

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A method to correlate the uninterpreted tandem mass spectra of peptides produced under low energy (lo-50 eV) collision conditions with amino acid sequences in the Genpept database has been developed. In this method the protein database is searched to identify linear amino acid sequences within a mass tolerance of * 1 u of the precursor ion molecular weight. A cross-correlation function is then used to provide a measurement of similarity between the mass-to-charge ratios for the fragment ions predicted from amino acid sequences obtained from the database and the fragment ions observed in the tandem mass spectrum. In general, a difference greater than 0.1 between the normalized cross-correlation functions of the first-and second-ranked search results indicates a successfol match between sequence and spectrum. Searches of species-specific protein databases with tandem mass spectra acquired from peptides obtained from the enzymatically digested total proteins of E. coli and S. cerevisiae cells allowed matchmg of the spectra to amino acid sequences within proteins of these organisms. The approach described in this manuscript provides a convenient method to interpret tandem mass spectra with known sequences in a protein database, fJ Am Sot Mass Spectrom 1994, 5, 976-989) A mino acid sequence analysis is often the initial step in characterizing a newly isolated protein.Conventional sequencing strategies employ chemical reagents to remove one amino acid at a time from the amino terminus followed by isolation and analysis of the released amino acid derivative [l, 21. Limitations in the chemical efficiency of the process prevents determination of the complete sequence of a protein from small quantities of sample. Partial sequence information, however, can be used to search a protein or nucleotide database to discover relationships to previously identified proteins or to determine if the protein sequence is novel 13, 41. Although sequence information may have been determined previously, the context in which the protein is identified may be relevant to the biological process under study [51. Another method to identify known protein sequences employs site-specific proteolysis followed by measurement of the mass-to-charge ratios of the pep tides by mass spectrometry. The set of observed peptide mass-to-charge ratios is then used to search a protein database to find a set of peptide masses predicted from enzymatic digestion of each protein in the database [6-101. Both chemical degradation and peptide mapping approaches require the use of fairly homogeneous samples to avoid ambiguity in assigning Address reprint requests to John R.

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Section: Application Of the Search Program To Singlementioning

confidence: 99%

An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database

Eng

McCormack

Yates

1994

J. Am. Soc. Mass Spectrom.

6,258

5,480

View full text Add to dashboard Cite

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“…5 and 43). The same mutation was recently confired in eight Finnish AGU patients also by others (6,44). The mutation, designated as AGUFil, causes a Cys163 --Ser change and results in the absence of a disulfide bridge in the AGA enzyme (5,7).…”

mentioning

confidence: 99%

Spectrum of mutations in aspartylglucosaminuria.

Ikonen

Aula

Grön

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Aspartyucaminuria (AGU) Is an inherited lysosomal storage disoder caused by the deficiency of aspartylguminidase. We have earlier reported a single missense mutation (Cys"*3 -~Ser) to be responsible for 98% of the AGU alleles in the isolated Finnish population, which contains about 90% of the reported AGU patients. Here we describe the spectrum of 10 AGU mutations found in unrelated patients of non-Finnish origin. Since 11 out of 12 AGU patients were homozygotes, con g ity has to be a common denominator in most AGU families. The mutations were distributed over the entire coding region of the aspartylgi cDNA, except in the carboxyl-terminal 17-kDa subunit in which they were clustered within a 46-amino acid region. Based on the character of the mutations, most of them are prone to affect the folding and stability and not to directly affect the active site of the aspartylglucosaminidase enzyme.

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“…John Yates and Pat Griffin pioneered the use of the mass spectrometer as a tool for protein and peptide identification and characterization. Yeats also developed some of the earliest computational proteomics techniques (54)(55)(56)(57). Also, we developed a pulse-field instrument for the size measurement of very large DNA fragments (58,59).…”

Section: New Strategies Employing the Four Instrumentsmentioning

confidence: 99%

A Personal Journey of Discovery: Developing Technology and Changing Biology

Hood

2008

Annual Rev. Anal. Chem.

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This autobiographical article describes my experiences in developing chemically based, biological technologies for deciphering biological information: DNA, RNA, proteins, interactions, and networks. The instruments developed include protein and DNA sequencers and synthesizers, as well as ink-jet technology for synthesizing DNA chips. Diverse new strategies for doing biology also arose from novel applications of these instruments. The functioning of these instruments can be integrated to generate powerful new approaches to cloning and characterizing genes from a small amount of protein sequence or to using gene sequences to synthesize peptide fragments so as to characterize various properties of the proteins. I also discuss the five paradigm changes in which I have participated: the development and integration of biological instrumentation; the human genome project; cross-disciplinary biology; systems biology; and predictive, personalized, preventive, and participatory (P4) medicine. Finally, I discuss the origins, the philosophy, some accomplishments, and the future trajectories of the Institute for Systems Biology.

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Aspartylglycosaminuria in the Finnish population: identification of two point mutations in the heavy chain of glycoasparaginase.

Cited by 46 publications

References 14 publications

An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database

An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database

Spectrum of mutations in aspartylglucosaminuria.

A Personal Journey of Discovery: Developing Technology and Changing Biology

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