The influence of amino acid substitutions on the conformational energy of cytochrome c.
Abstract: Conformational energies have been evaluated for each of the staggered side-chain conformations associated with the 261 amino acid substitutions known to occur among 60 eucaryotic species. At least 86% of these substitutions can be sterically accommodated (one at a time) within the structure of horse-heart cytochrome c resulting from conformational energy refinement. Simultaneous incorporation of all pertinent amino acid substitutions found in eight representative species into the refined horse-heart structure is also shown to be sterically possible, with few exceptions. In two cases (Pekin duck cytochrome with 10 substitutions and Samia cynthia cytochrome with 24 substitutions), all substitutions could be readily incorporated, and the total energies associated with their computed structures differed by less than 10 kcal/mol from that of horse-heart cytochrome c. In the cytochromes from rattlesnake (22 substitutions), tuna (18 substitutions), and Neurospora crassa (36 substitutions), tyrosine could not be substituted for phenylalanine at position 46, within the constraints of the calculations. However, when all of the remaining substitutions were incorporated into these three cytochromes, their computed conformational energies differed by less than 30 kcal/mol from that of horse-heart cytochrome c. Between two and four amino acid substitutions cause high energies in the cytochromes from human, baker's yeast, and cotton seed, but all of the remaining substitutions are consistent with a low energy conformation. These results suggest that the structures of homologous proteins may be even more similar than has previously been recognized. Substitutions of all possible amino acid types at the invariant positions (where all eucaryotic cytochromes c bear the same amino acid) have revealed some cases where different amino acids can be accommodated, thus demonstrating that the biological constraints on amino acid substitutions are often different from the purely steric constraints investigated in this work.
Publication Date: 1975-08-12 PubMed ID: 169879DOI: 10.1021/bi00687a002Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This study investigates how changes in amino acids influence the conformational energy of cytochrome c, a protein found within cells. By analyzing 261 known amino acid substitutions across 60 different species, the researchers found that most changes were able to be absorbed structurally by the cytochrome c of horses’ hearts, and that structures of similar proteins may be more alike than previously anticipated.
Understanding Amino Acid Substitutions
- The researchers evaluated the conformational energies for expanded patterns of side-chain formations in over 261 known amino acid substitutions occurring in a diverse group of sixty eukaryotic species. Conformational energy relates to the shape of a protein and how it forms that shape.
- The focus was mainly on amino acid substitutions that can be managed within the structure of horse-heart cytochrome c, a specific model system of the cytochrome protein class widely used in protein structure research. They found that nearly 86% of the substitutions could be structurally accommodated.
Simultaneous Incorporation Of Substitutions
- The researchers also determined that it’s possible to incorporate all of the significant amino acid substitutions found in eight different species into the refined horse-heart structure, with minor exceptions.
- There were a couple of exceptions in cases where specific substitutions could not be implemented. For instance, in the cytochromes of rattlesnake, tuna, and a specific fungus species, one specific substitution could not occur reliably within the study parameters.
Impact Of Substitutions On Energetic Profile Of Proteins
- In most cases, the total energies associated with the computed structures differed by less than 30 kcal/mol from that of horse-heart cytochrome c, even after incorporating all substitutions. This indicates the structural flexibility of proteins to incorporate and adapt to amino acid substitutions.
- The study indicated that a few amino acid substitutions could cause high energies in the proteins from humans, baker’s yeast, and cotton seed. However, the remaining substitutions appeared to espouse a low energy conformation, suggesting a level of adaptability and resilience in cytochrome c proteins to specific amino acid substitutions.
Further Implications
- This research suggests that the structural similarity among homologous proteins may be higher than previously believed, demonstrating the innate flexibility and compatibility of these protein structures.
- A side observation showed that the biological constraints on amino acid changes often differed from the purely steric or spatial constraints explored in this study, signalling the need for more nuanced research into the effects of these changes on protein structures and functionality.
Cite This Article
APA
Warme PK.
(1975).
The influence of amino acid substitutions on the conformational energy of cytochrome c.
Biochemistry, 14(16), 3518-3526.
https://doi.org/10.1021/bi00687a002 Publication
Researcher Affiliations
MeSH Terms
- Amino Acid Sequence
- Amino Acids / analysis
- Animals
- Binding Sites
- Calorimetry
- Cytochrome c Group
- Horses
- Lysine / analysis
- Methylation
- Myocardium / enzymology
- Protein Binding
- Protein Conformation
- Thermodynamics
- X-Ray Diffraction
Citations
This article has been cited 3 times.- Pfeil W. The problem of the stability globular proteins.. Mol Cell Biochem 1981 Oct 9;40(1):3-28.
- Kolchanov NA, Shindyalov IN. Single amino acid substitutions producing instability of globular proteins. Calculation of their frequencies in the entire mutational spectra of the alpha- and beta-subunits of human hemoglobin.. J Mol Evol 1988;27(2):154-62.
- Llinás M, Neilands JB. The structure of two alanine containing ferrichromes: sequence determination by proton magnetic resonance.. Biophys Struct Mech 1976 Aug 23;2(2):105-17.
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