Peptide models XLV: Conformational properties of N-formyl-L-methioninamide and its relevance to methionine in proteins

András Láng, I. Csizmadia, A. Perczel

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9 Citations (Scopus)

Abstract

The conformational space of the most biologically significant backbone folds of a suitable methionine peptide model was explored by density functional computational method. Using a medium [6-31G(d)] and a larger basis set [6-311++G(2d,2p)], the systematic exploration of low-energy backbone structures restricted for the "L-region" in the Ramachandran map of N-formyl-L-methioninamide results in conformers corresponding to the building units of an extended backbone structure (βL), an inverse γ-turn (γL), or a right-handed helical structure (αL). However, no poly-proline II type (εL) fold was found, indicating that this conformer has no intrinsic stability, and highlighting the effect of molecular environment in stabilizing this backbone structure. This is in agreement with the abundance of the εL- type backbone conformation of methionine found in proteins. Stability properties (ΔE) and distinct backbone-sidechain interactions support the idea that specific intramolecular contacts are operative in the "selection" of the lowest energy conformers. Apart from the number of different folds, all stable conformers are within a 10 kcal.mol-1 energy range, indicating the highly flexible behavior of methionine. This conformational feature can be important in supporting catalytic processes, facilitating protein folding and dimerization via metal ion binding. In both of the biological examples discussed (HIV-1 reverse transcriptase and PcoC copper-resistant protein), the conformational properties of Met residues were found to be of key importance. Spatial proximity to other types of residues or the same type of residue seems to be crucial for the structural integrity of a protein, whether Met is buried or exposed.

Original languageEnglish
Pages (from-to)571-588
Number of pages18
JournalProteins: Structure, Function and Genetics
Volume58
Issue number3
DOIs
Publication statusPublished - Feb 15 2005

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Methionine
Peptides
Protein Multimerization
Protein folding
Proteins
Dimerization
Protein Folding
Structural integrity
Computational methods
Proline
Metal ions
Conformations
Copper
Metals
Ions
methioninamide
Human immunodeficiency virus 1 reverse transcriptase
polyproline

Keywords

  • Amino acid derivatives
  • Conformation analysis
  • DFT computations
  • Methionine
  • Peptide model

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

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title = "Peptide models XLV: Conformational properties of N-formyl-L-methioninamide and its relevance to methionine in proteins",
abstract = "The conformational space of the most biologically significant backbone folds of a suitable methionine peptide model was explored by density functional computational method. Using a medium [6-31G(d)] and a larger basis set [6-311++G(2d,2p)], the systematic exploration of low-energy backbone structures restricted for the {"}L-region{"} in the Ramachandran map of N-formyl-L-methioninamide results in conformers corresponding to the building units of an extended backbone structure (βL), an inverse γ-turn (γL), or a right-handed helical structure (αL). However, no poly-proline II type (εL) fold was found, indicating that this conformer has no intrinsic stability, and highlighting the effect of molecular environment in stabilizing this backbone structure. This is in agreement with the abundance of the εL- type backbone conformation of methionine found in proteins. Stability properties (ΔE) and distinct backbone-sidechain interactions support the idea that specific intramolecular contacts are operative in the {"}selection{"} of the lowest energy conformers. Apart from the number of different folds, all stable conformers are within a 10 kcal.mol-1 energy range, indicating the highly flexible behavior of methionine. This conformational feature can be important in supporting catalytic processes, facilitating protein folding and dimerization via metal ion binding. In both of the biological examples discussed (HIV-1 reverse transcriptase and PcoC copper-resistant protein), the conformational properties of Met residues were found to be of key importance. Spatial proximity to other types of residues or the same type of residue seems to be crucial for the structural integrity of a protein, whether Met is buried or exposed.",
keywords = "Amino acid derivatives, Conformation analysis, DFT computations, Methionine, Peptide model",
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T2 - Conformational properties of N-formyl-L-methioninamide and its relevance to methionine in proteins

AU - Láng, András

AU - Csizmadia, I.

AU - Perczel, A.

PY - 2005/2/15

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N2 - The conformational space of the most biologically significant backbone folds of a suitable methionine peptide model was explored by density functional computational method. Using a medium [6-31G(d)] and a larger basis set [6-311++G(2d,2p)], the systematic exploration of low-energy backbone structures restricted for the "L-region" in the Ramachandran map of N-formyl-L-methioninamide results in conformers corresponding to the building units of an extended backbone structure (βL), an inverse γ-turn (γL), or a right-handed helical structure (αL). However, no poly-proline II type (εL) fold was found, indicating that this conformer has no intrinsic stability, and highlighting the effect of molecular environment in stabilizing this backbone structure. This is in agreement with the abundance of the εL- type backbone conformation of methionine found in proteins. Stability properties (ΔE) and distinct backbone-sidechain interactions support the idea that specific intramolecular contacts are operative in the "selection" of the lowest energy conformers. Apart from the number of different folds, all stable conformers are within a 10 kcal.mol-1 energy range, indicating the highly flexible behavior of methionine. This conformational feature can be important in supporting catalytic processes, facilitating protein folding and dimerization via metal ion binding. In both of the biological examples discussed (HIV-1 reverse transcriptase and PcoC copper-resistant protein), the conformational properties of Met residues were found to be of key importance. Spatial proximity to other types of residues or the same type of residue seems to be crucial for the structural integrity of a protein, whether Met is buried or exposed.

AB - The conformational space of the most biologically significant backbone folds of a suitable methionine peptide model was explored by density functional computational method. Using a medium [6-31G(d)] and a larger basis set [6-311++G(2d,2p)], the systematic exploration of low-energy backbone structures restricted for the "L-region" in the Ramachandran map of N-formyl-L-methioninamide results in conformers corresponding to the building units of an extended backbone structure (βL), an inverse γ-turn (γL), or a right-handed helical structure (αL). However, no poly-proline II type (εL) fold was found, indicating that this conformer has no intrinsic stability, and highlighting the effect of molecular environment in stabilizing this backbone structure. This is in agreement with the abundance of the εL- type backbone conformation of methionine found in proteins. Stability properties (ΔE) and distinct backbone-sidechain interactions support the idea that specific intramolecular contacts are operative in the "selection" of the lowest energy conformers. Apart from the number of different folds, all stable conformers are within a 10 kcal.mol-1 energy range, indicating the highly flexible behavior of methionine. This conformational feature can be important in supporting catalytic processes, facilitating protein folding and dimerization via metal ion binding. In both of the biological examples discussed (HIV-1 reverse transcriptase and PcoC copper-resistant protein), the conformational properties of Met residues were found to be of key importance. Spatial proximity to other types of residues or the same type of residue seems to be crucial for the structural integrity of a protein, whether Met is buried or exposed.

KW - Amino acid derivatives

KW - Conformation analysis

KW - DFT computations

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