Solution NMR evidence for a cis Tyr-Ala peptide group in the structure of [Pro93Ala] bovine pancreatic ribonuclease A

Ying Xiong, Darmawi Juminaga, G. V.T. Swapna, William J. Wedemeyer, Harold A. Scheraga, Gaetano T. Montelione

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17 Scopus citations


Proline peptide group isomerization can result in kinetic barriers in protein folding. In particular, the cis proline pep- tide conformation at Tyr92-Pro93 of bovine pancreatic ribonuclease A (RNase A) has been proposed to be crucial for chain folding initiation. Mutation of this proline-93 to alanine results in an RNase A molecule, P93A, that exhibits unfolding/refolding kinetics consistent with a cis Tyr92-Ala93 peptide group conformation in the folded structure (Dodge RW, Scheraga HA, 1996, Biochemistry 35:1548-1559). Here, we describe the analysis of backbone proton resonance assignments for P93A together with nuclear Overhauser effect data that provide spectroscopic evidence for a type VI β-bend conformation with a cis Tyr92-Ala93 peptide group in the folded structure. This is in contrast to the reported X-ray crystal structure of [Pro93Gly]-RNase A (Schultz LW, Hargraves SR, Klink TA, Raines RT, 1998. Protein Sci 7:1620-1625), in which Tyr92- Gly93 forms a type-II β-bend with a trans peptide group conformation. While a glycine residue at position 93 accommodates a type II bend (with a positive value of φ93), RNase A molecules with either proline or alanine residues at this position appear to require a cis peptide group with a type- Vl β-bend for proper folding. These results support the view that a cis Pro93 conformation is crucial for proper folding of wild-type RNase A.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalProtein Science
Issue number2
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


  • Cis peptide groups
  • Protein NMR
  • Protein folding mechanisms


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