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Hot Electron Capture Dissociation Distinguishes Leucine from Isoleucine in a Novel Hemoglobin Variant, Hb Askew, β54(D5)Val→Ile

Williams, Jonathan P. and Creese, Andrew J. and Roper, David R. and Green, Brian N. and Cooper, Helen J. (2009) Hot Electron Capture Dissociation Distinguishes Leucine from Isoleucine in a Novel Hemoglobin Variant, Hb Askew, β54(D5)Val→Ile. Journal of the American Society for Mass Spectrometry, 20 (9). p. 1707. ISSN 10440305

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URL of Published Version: http://dx.doi.org/10.1016/j.jasms.2009.05.002

Identification Number/DOI: doi:10.1016/j.jasms.2009.05.002

Population migration has led to the global dispersion of human hemoglobinopathies and has precipitated a need for their identification. An effective mass spectrometry-based procedure involves analysis of the intact α- and β-globin chains to determine their mass, followed by location of the variant amino acid residue by direct analysis of the enzymatically digested chains and low-energy collision induced dissociation of the variant peptide. Using this procedure, a variant was identified as either β54Val→Leu or β54Val→Ile, since the amino acids leucine and isoleucine cannot be distinguished using low-energy collisions. Here, we describe how hot electron capture dissociation on a Fourier transform-ion cyclotron resonance mass spectrometer was used to distinguish isoleucine from leucine and identify the mutation as β54(D5)Val→Ile. This is a novel variant, and we have named it Hb Askew.

Type of Work:Article
Date:2009 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:Biosciences
Subjects:QR Microbiology
Institution:University of Birmingham
Copyright Holders:American Society for Mass Spectronomy
ID Code:396
Refereed:YES
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