Hyperfine-shifted 13C resonance assignments in an iron-sulfur protein with quantum chemical verification: Aliphatic C-H⋯S 3-center-4-electron interactions

William M. Westler, I. Jin Lin, A. Perczel, Frank Weinhold, John L. Markley

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Although the majority of noncovalent interactions associated with hydrogen and heavy atoms in proteins and other biomolecules are classical hydrogen bonds between polar N-H or O-H moieties and O atoms or aromatic π electrons, high-resolution X-ray crystallographic models deposited in the Protein Data Bank show evidence for weaker C-H⋯O hydrogen bonds, including ones involving sp3-hybridized carbon atoms. Little evidence is available in proteins for the (even) weaker C-H⋯S interactions described in the crystallographic literature on small molecules. Here, we report experimental evidence and theoretical verification for the existence of nine aliphatic (sp3-hybridized) C-H⋯S 3-center-4-electron interactions in the protein Clostridium pasteurianum rubredoxin. Our evidence comes from the analysis of carbon-13 NMR chemical shifts assigned to atoms near the iron at the active site of this protein. We detected anomalous chemical shifts for these carbon-13 nuclei and explained their origin in terms of unpaired spin density from the iron atom being delocalized through interactions of the type: C-H⋯S-Fe, where S is the sulfur of one of the four cysteine side chains covalently bonded to the iron. These results suggest that polarized sulfur atoms in proteins can engage in multiple weak interactions with surrounding aliphatic groups. We analyze the strength and angular dependence of these interactions and conclude that they may contribute small, but significant, stabilization to the molecule.

Original languageEnglish
Pages (from-to)1310-1316
Number of pages7
JournalJournal of the American Chemical Society
Volume133
Issue number5
DOIs
Publication statusPublished - Feb 9 2011

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Iron-Sulfur Proteins
Sulfur
Electrons
Iron
Proteins
Atoms
Hydrogen
Carbon
Chemical shift
Hydrogen bonds
Clostridium
Molecules
Biomolecules
Cysteine
Catalytic Domain
X-Rays
HS 3
Databases
Stabilization
Nuclear magnetic resonance

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Hyperfine-shifted 13C resonance assignments in an iron-sulfur protein with quantum chemical verification : Aliphatic C-H⋯S 3-center-4-electron interactions. / Westler, William M.; Lin, I. Jin; Perczel, A.; Weinhold, Frank; Markley, John L.

In: Journal of the American Chemical Society, Vol. 133, No. 5, 09.02.2011, p. 1310-1316.

Research output: Contribution to journalArticle

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