O2 binding to human serum albumin incorporating iron porphyrin with a covalently linked methyl-L-histidine isomer.
We describe the significant difference in the O2 binding affinities of human serum albumin (HSA) incorporating 5,10,15,20-tetrakis{alpha,alpha,alpha,alpha- o-(1'-methylcyclohexanamido)phenyl}porphinatoiron(II) with a covalently linked 1-methyl-L-histidine or 3-methyl-L-histidine [HSA-FeP(1-MHis), HSA-FeP(3-MHis)]. The HSA-FeP(3-MHis) showed an extraordinarily high O2 binding affinity ( P1/2 = 0.2 Torr, 25 degrees C, pH 7.4), which is close to those of relaxed-state hemoglobin and myoglobin. However, replacement of the 3-methyl-L-histidine moiety in FeP(3-MHis) by 1-methyl-L-histidine caused a 35-fold reduction in O2 affinity; the P 1/2 value of HSA-FeP(1-MHis) (22 Torr, 37 degrees C, pH 7.4) is almost identical to that of human red blood cells. Results of kinetic studies indicate that the low O2 binding affinity of FeP(1-MHis) is predominantly manifested in the high O2 dissociation rate constant. In a toluene solution, an identical relationship in the O2 binding property was similarly observed for FeP(1-MHis) and FeP(3-MHis). The axial Fe-N(1-MHis) coordination might be restrained by steric interaction between the 4-methylene group of the histidine and the porphyrin plane.
Nakagawa
Akito
A
Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Komatsu
Teruyuki
T
Iizuka
Makoto
M
Tsuchida
Eishun
E
D007202:Indicators and Reagents; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D008762:Methylhistidines / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry*; D010782:Photolysis; D011166:Porphyrins / Q000737:chemistry*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D007202:Indicators and Reagents; D008762:Methylhistidines; D011166:Porphyrins; D012709:Serum Albumin; D007501:Iron; D010100:Oxygen