Solution NMR determination of the seating(s) of meso-nitro-etioheme-1 in myoglobin: implications for steric constraints to meso position access in heme degradation by coupled oxidation.
Abstract: The highly stereoselective cleavage of hemin in myoglobin by coupled oxidation has been attributed to steric barriers that leave more space near the alpha- than the other meso-positions. The steric barriers near meso positions in myoglobin have been investigated by establishing the thermodynamics and dynamics of possible seatings in the pocket of horse myoglobin of a four-fold symmetric etioheme I modified with a bulky nitro group at a single meso position. The cyanomet complex of this reconstituted myoglobin exhibits three sets of (1)H NMR resonances that are linked dynamically and occur in approximate populations ratios of 0.82:0.10:0.08. Two dimensional (1)H NMR has been used to assign the hemin and heme pocket resonances in the major isomer in solution and to determine that the hemin is oriented with the nitro group at the canonical gamma-meso position of native hemin. The dominance of this isomer is attributed to the solvent exposure of this portion of the hemin which stabilizes the highly polar nitro group. Using a combination of magnetization transfer among methyl groups of the three isomers due to "hopping" of the hemin about its normal, the assigned resonances of an isoelectronic, bis-cyano complex of meso-nitro-etioheme I, and the known essentially constant rhombic perturbation of heme pocket sites on the hyperfine shifts of heme methyl (Kolczak, U.; Hauksson, J. B.; Davis, N. L.; Pande, U.; de Ropp, J. S.; Langry, K. C.; Smith, K. M.; LaMar, G. N. J. Am. Chem. Soc. 1999, 121, 835-843); the two minor isomers are shown to place their bulky nitro group at the canonical delta-meso (8%) and alpha-meso positions (10%). The comparable population of the isomers with nitro groups at the hydrophobic alpha- and delta-meso positions dictates that, while the static crystal structure finds more room near the alpha-meso position, the deformation at minimal energetic expense near the alpha- and delta-meso positions is comparable. These results argue that factors other than simple steric influences control the selectivity of the ring cleavage in myoglobin.
Publication Date: 2001-08-17 PubMed ID: 11506564DOI: 10.1021/ja010651aGoogle Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research explores the cleavage of hemin in myoglobin by studying the steric barriers. Scientists use a modified four-fold symmetric etioheme I and determine how it settles in a horse myoglobin pocket. The findings suggest that elements other than basic steric effects control how the ring is cleaved in myoglobin.
Understanding Hemin Cleavage
- The report probes the highly stereoselective cleavage of hemin in myoglobin, a process previously linked to steric barriers leading to more room near alpha- than other meso-positions.
- Steric barriers close to meso positions are examined through the mapping of the thermodynamics and dynamics of potential seatings of a modified etioheme I in the pocket of horse myoglobin.
Key Investigations and Techniques
- The cyanomet complex of reconstituted myoglobin, characterized by three sets of 1H NMR resonances, linked dynamically, is a focal point of this research.
- Two-dimensional 1H NMR was employed to assign hemin and heme pocket resonances in the primary isomer in solution. This method was also used to reveal the orientation of hemin, specifically showing the nitro group at the gamma-meso position of native hemin.
- The magnetization transfer, or “hopping”, of the hemin about its axis among the three isomers, the assigned resonances of an isoelectronic, bis-cyano complex of meso-nitro-etioheme I, and the known fixed rhombic perturbation of heme pocket sites informed the research.
Key Findings
- Two minor isomers positioning their bulky nitro group at the canonical delta-meso (8%) and alpha-meso positions (10%) are revealed.
- The alpha- and delta-meso populated isomers with nitro groups indicated that, despite the static crystal structure providing more room near the alpha-meso position, the deformation with minimum energy loss near the alpha- and delta-meso positions are similar.
- These outcomes argue that factors beyond ordinary steric influences control the selectivity of the ring cleavage in myoglobin. Thus the complexities of the cleavage of hemin in myoglobin are enhanced by these findings, revealing multiple influential factors.
Cite This Article
APA
Wang J, Li Y, Ma D, Kalish H, Balch AL, La Mar GN.
(2001).
Solution NMR determination of the seating(s) of meso-nitro-etioheme-1 in myoglobin: implications for steric constraints to meso position access in heme degradation by coupled oxidation.
J Am Chem Soc, 123(33), 8080-8088.
https://doi.org/10.1021/ja010651a Publication
Researcher Affiliations
- Department of Chemistry, University of California, Davis, California 95616, USA.
MeSH Terms
- Animals
- Apoproteins / chemistry
- Bone and Bones
- Chemical Phenomena
- Chemistry, Physical
- Cyclization
- Heme / chemistry
- Heme Oxygenase (Decyclizing) / metabolism
- Hemin / analogs & derivatives
- Hemin / chemistry
- Horses
- Magnetic Resonance Spectroscopy
- Models, Chemical
- Molecular Structure
- Myoglobin / chemistry
- Myoglobin / metabolism
- Oxidation-Reduction
- Pyrroles / chemistry
- Stereoisomerism
- Structure-Activity Relationship
Grant Funding
- GM26226 / NIGMS NIH HHS
- GM62830 / NIGMS NIH HHS
- HL16087 / NHLBI NIH HHS
- RR04795 / NCRR NIH HHS
- RR08206 / NCRR NIH HHS
- RR11973 / NCRR NIH HHS
Citations
This article has been cited 2 times.- Walker FA. The heme environment of mouse neuroglobin: histidine imidazole plane orientations obtained from solution NMR and EPR spectroscopy as compared with X-ray crystallography.. J Biol Inorg Chem 2006 Jun;11(4):391-7.
- Bondarenko V, Wang J, Kalish H, Balch AL, La Mar GN. Solution 1H NMR study of the accommodation of the side chain of n-butyl-etiohemin-I incorporated into the active site of cyano-metmyoglobin.. J Biol Inorg Chem 2005 May;10(3):283-93.
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