Contribution of heme-propionate side chains to structure and function of myoglobin: chemical approach by artificially created prosthetic groups.
Horse heart myoglobin was reconstituted with mesohemin derivatives methylated at the 6- or 7-position to evaluate the role of the heme-6-propionate or heme-7-propionate side chain in the protein. The association and dissociation of the O(2) binding for the deoxymyoglobin with 6-methyl-7-propionate mesoheme are clearly accelerated. Furthermore, the myoglobin with 6-methyl-7-propionate mesoheme shows fast autoxidation from oxymyoglobin to metmyoglobin compared to the myoglobin with 6-propionate-7-methyl heme and the reference protein. These results indicate the 6-propionate plays an important physiological role in the stabilization of oxymyoglobin because of the formation of a salt-bridge with the Lys45. The acceleration of CO binding rate is observed for the myoglobin with 6-propionate-7-methyl mesoheme, suggesting that the replacement of the 7-propionate with a methyl group has an influence on the His93-heme iron coordination. The structural perturbation of His93 imidazole was also supported by 1H NMR spectra of cyanide and deoxy forms of the myoglobin with 6-propionate-7-methyl mesoheme. Thus, it is found that the 7-propionate regulates the hydrogen-bonding network and His93-heme iron coordination in the proximal site.
Hayashi
Takashi
T
Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, Fukuoka 812-8581, Japan. thayatcm@mbox.nc.kyushu-u.ac.jp
Matsuo
Takashi
T
Hitomi
Yutaka
Y
Okawa
Kazufumi
K
Suzuki
Akihiro
A
Shiro
Yoshitsugu
Y
Iizuka
Tetsutaro
T
Hisaeda
Yoshio
Y
Ogoshi
Hisanobu
H
D000818:Animals; D001665:Binding Sites; D002248:Carbon Monoxide / Q000378:metabolism; D003486:Cyanides / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D006736:Horses; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009206:Myocardium / Q000737:chemistry; D009211:Myoglobin / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D003486:Cyanides; D009211:Myoglobin; C081433:heme propionate-7; D006418:Heme; D002248:Carbon Monoxide; D010100:Oxygen