Site-specific modification of positively-charged surfaces on human serum albumin by malondialdehyde.
Malondialdehyde (MDA), a lipid peroxidation product, reacts with lysine residues in proteins. Human serum albumin (HSA) is a major target of MDA-modification of serum proteins. To identify, the modification sites of HSA by MDA in vitro, MDA-treated HSA was digested with a protease and the resulting peptides were subjected to liquid chromatography-tandem mass spectrometry. We identified six peptides, which contained a N-propenal adduct at Lys136, Lys174, Lys240, Lys281, Lys525, and Lys541, and revealed that Lys525 is the most reactive residue for MDA modification. Analysis of electrostatic surface potential of a 3-D model structure of HSA indicates that Lys525 is located at the center of positively charged grooves. The results of this study indicate that the modification of proteins by lipid-derived aldehydes may be influenced by the electrostatic potential of the protein surface.
Ishii
Takeshi
T
Department of Food and Nutritional Sciences, and Global COE Program, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Ito
Sohei
S
Kumazawa
Shigenori
S
Sakurai
Toyo
T
Yamaguchi
Satoru
S
Mori
Taiki
T
Nakayama
Tsutomu
T
Uchida
Koji
K
D000595:Amino Acid Sequence; D002853:Chromatography, Liquid; D006801:Humans; D008239:Lysine / Q000032:analysis; D008315:Malondialdehyde / Q000737:chemistry*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry*; D055672:Static Electricity; D053719:Tandem Mass Spectrometry
D010446:Peptide Fragments; D012709:Serum Albumin; D008315:Malondialdehyde; D010447:Peptide Hydrolases; D008239:Lysine