Contribution of heme-propionate side chains to structure and function of myoglobin: chemical approach by artificially created prosthetic groups.
Abstract: 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.
Publication Date: 2002-07-18 PubMed ID: 12121766DOI: 10.1016/s0162-0134(02)00423-3Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers examined the role of certain side chains in myoglobin, a protein in heart muscle, by artificially modifying them and observing changes in oxygen binding and oxidation rates. They found that these modifications affected physiological functions and structural aspects of the protein, confirming the importance of heme-propionate side chains.
The Objective and Method of the Research
- The goal of the study was to understand the role of heme-propionate side chains in the structure and function of myoglobin, a protein found in heart muscle.
- Researchers aimed to uncover this by studying myoglobin reconstituted with mesohemin derivatives – known as artificial prosthetic groups. These groups were specifically methylated, or modified, at either the 6th or 7th position.
The Role of 6-Propionate and 7-Propionate in Myoglobin
- The study’s results showed that 6-propionate plays a vital role in stabilizing oxymyoglobin due to the formation of a salt-bridge with Lysine at position 45 (Lys45).
- It was also observed that alterations to 6-propionate rapidly accelerated the binding rate of carbon monoxide (CO) in myoglobin.
- Similarly, the replacement of the 7-propionate with a methyl group influenced the coordination between Histidine at position 93 (His93) and heme iron, reflecting 7-propionate’s control over the hydrogen-bonding network and heme iron coordination.
Supporting Evidence from Spectral Analysis
- This role of 7-propionate was further reinforced by spectral observations derived from 1H NMR spectroscopy. Structural changes in His93’s imidazole, a compound forming part of histidine, were noted in the spectra when observing cyanide and deoxy forms of myoglobin with 6-propionate-7-methyl mesoheme.
Important Findings and Conclusion
- The modification of myoglobin with 6-methyl-7-propionate mesoheme led to a clear acceleration in the association and dissociation of oxygen binding. In addition, rapid autoxidation from oxymyoglobin to metmyoglobin was observed, compared to those of myoglobin carrying 6-propionate-7-methyl heme and the reference protein.
- The overall findings reveal that heme-propionate side chains, particularly 6-propionate and 7-propionate, significantly contribute to the overall structure and function of myoglobin protein.
Cite This Article
APA
Hayashi T, Matsuo T, Hitomi Y, Okawa K, Suzuki A, Shiro Y, Iizuka T, Hisaeda Y, Ogoshi H.
(2002).
Contribution of heme-propionate side chains to structure and function of myoglobin: chemical approach by artificially created prosthetic groups.
J Inorg Biochem, 91(1), 94-100.
https://doi.org/10.1016/s0162-0134(02)00423-3 Publication
Researcher Affiliations
- Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, Fukuoka 812-8581, Japan. thayatcm@mbox.nc.kyushu-u.ac.jp
MeSH Terms
- Animals
- Binding Sites
- Carbon Monoxide / metabolism
- Cyanides / metabolism
- Heme / analogs & derivatives
- Heme / chemistry
- Heme / metabolism
- Horses
- Magnetic Resonance Spectroscopy
- Models, Molecular
- Molecular Structure
- Myocardium / chemistry
- Myoglobin / chemistry
- Myoglobin / metabolism
- Oxidation-Reduction
- Oxygen / metabolism
- Protein Binding
- Protein Structure, Tertiary
Citations
This article has been cited 4 times.- Carminati DM, Moore EJ, Fasan R. Strategies for the expression and characterization of artificial myoglobin-based carbene transferases.. Methods Enzymol 2020;644:35-61.
- Nagai M, Mizusawa N, Kitagawa T, Nagatomo S. A role of heme side-chains of human hemoglobin in its function revealed by circular dichroism and resonance Raman spectroscopy.. Biophys Rev 2018 Apr;10(2):271-284.
- Ramos-Santana BJ, López-Garriga J. Tyrosine B10 triggers a heme propionate hydrogen bonding network loop with glutamine E7 moiety.. Biochem Biophys Res Commun 2012 Aug 10;424(4):771-6.
- Garcia-Serres R, Davydov RM, Matsui T, Ikeda-Saito M, Hoffman BM, Huynh BH. Distinct reaction pathways followed upon reduction of oxy-heme oxygenase and oxy-myoglobin as characterized by Mössbauer spectroscopy.. J Am Chem Soc 2007 Feb 7;129(5):1402-12.
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