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PMID:1540659

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Citation

Wajcman, H, Kister, J, Vasseur, C, Blouquit, Y, Trastour, JC, Cottenceau, D and Galacteros, F (1992) Structure of the EF corner favors deamidation of asparaginyl residues in hemoglobin: the example of Hb La Roche-sur-Yon [beta 81 (EF5) Leu----His]. Biochim. Biophys. Acta 1138:127-32

Abstract

Some abnormal hemoglobins constitute models which allow one to evaluate the structural requirements for post-translational modifications in proteins, such as deamidation. Hb La Roche-sur-Yon [beta 81 (EF5) Leu----His] is an unstable hemoglobin variant displaying a moderately increased oxygen affinity. About half of the abnormal hemoglobin, in addition to the substitution at position beta 81, carries a deamidation of the neighboring asparagine residue, beta 80 (EF4). The histidine at position beta 81 cannot fit into the small hydrophobic pocket which normally accomodates the leucine residue. This structural change opens the heme pocket and modifies the general conformation of the EF segment, thus explaining the increase in oxygen affinity and the achievement of a three-dimensional structure favoring asparagine deamidation. Histidine beta 81 could also act as a catalyst in the deamidation reaction. Deamidation has already been reported for two other variants of the EF corner, Hb Providence [beta 82 (EF6) Lys----Asn] and Hb J Singapore [alpha 79 (EF8) Ala----Gly]. In all these cases it seems that a histidine may catalyze the deamidation of the asparagine residues and that disturbing the folding of the EF corner will provide an extra flexibility favoring the reaction.

Links

PubMed

Keywords

Adolescent; Amino Acid Sequence; Asparagine/metabolism; Chromatography, High Pressure Liquid; Female; Hemoglobins, Abnormal/genetics; Hemoglobins, Abnormal/metabolism; Histidine/genetics; Humans; Isoelectric Focusing; Leucine/genetics; Models, Molecular; Molecular Sequence Data; Oxygen/metabolism; Protein Conformation; Protein Processing, Post-Translational

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:HBB

involved_in

GO:0015671: oxygen transport

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HBB

part_of

GO:0005833: hemoglobin complex

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete


See also

References

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