PDBsum entry 1d5d

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Hydrolase PDB id
Protein chains
15 a.a.
101 a.a. *
Waters ×138
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: The role of phenylalanine 8 in the stabilization of the s protein-s peptide interaction: packing and cavities
Structure: S peptide. Chain: a. Fragment: residues 1-15. Engineered: yes. Mutation: yes. Other_details: synthetic. Rnase s. Chain: b. Fragment: residues 21-124
Source: Synthetic: yes. Other_details: s15 peptide synthesized by solid phase peptide synthesis. Bos taurus. Cattle. Organism_taxid: 9913. Other_details: derieved from a limit digest of bovine pancreatic rnase a
Biol. unit: Dimer (from PQS)
2.25Å     R-factor:   0.189     R-free:   0.218
Authors: G.S.Ratnaparkhi,R.Varadarajan
Key ref:
G.S.Ratnaparkhi and R.Varadarajan (2000). Thermodynamic and structural studies of cavity formation in proteins suggest that loss of packing interactions rather than the hydrophobic effect dominates the observed energetics. Biochemistry, 39, 12365-12374. PubMed id: 11015216 DOI: 10.1021/bi000775k
07-Oct-99     Release date:   20-Oct-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic
150 a.a.
15 a.a.*
Protein chain
Pfam   ArchSchema ?
P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic
150 a.a.
101 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Pancreatic ribonuclease.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     nucleic acid binding     1 term  


DOI no: 10.1021/bi000775k Biochemistry 39:12365-12374 (2000)
PubMed id: 11015216  
Thermodynamic and structural studies of cavity formation in proteins suggest that loss of packing interactions rather than the hydrophobic effect dominates the observed energetics.
G.S.Ratnaparkhi, R.Varadarajan.
The hydrophobic effect is widely believed to be an important determinant of protein stability. However, it is difficult to obtain unambiguous experimental estimates of the contribution of the hydrophobic driving force to the overall free energy of folding. Thermodynamic and structural studies of large to small substitutions in proteins are the most direct method of measuring this contribution. We have substituted the buried residue Phe8 in RNase S with alanine, methionine, and norleucine. Binding thermodynamics and structures were characterized by titration calorimetry and crystallography, respectively. The crystal structures of the RNase S F8A, F8M, and F8Nle mutants indicate that the protein tolerates the changes without any main chain adjustments. The correlation of structural and thermodynamic parameters associated with large to small substitutions was analyzed for nine mutants of RNase S as well as 32 additional cavity-containing mutants of T4 lysozyme, human lysozyme, and barnase. Such substitutions were typically found to result in negligible changes in DeltaC(p)() and positive values of both DeltaDeltaH degrees and DeltaDeltaS of folding. Enthalpic effects were dominant, and the sign of DeltaDeltaS is the opposite of that expected from the hydrophobic effect. Values of DeltaDeltaG degrees and DeltaDeltaH degrees correlated better with changes in packing parameters such as residue depth or occluded surface than with the change in accessible surface area upon folding. These results suggest that the loss of packing interactions rather than the hydrophobic effect is a dominant contributor to the observed energetics for large to small substitutions. Hence, estimates of the magnitude of the hydrophobic driving force derived from earlier mutational studies are likely to be significantly in excess of the actual value.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21377472 C.N.Pace, H.Fu, K.L.Fryar, J.Landua, S.R.Trevino, B.A.Shirley, M.M.Hendricks, S.Iimura, K.Gajiwala, J.M.Scholtz, and G.R.Grimsley (2011).
Contribution of hydrophobic interactions to protein stability.
  J Mol Biol, 408, 514-528.  
20635344 R.L.Baldwin, C.Frieden, and G.D.Rose (2010).
Dry molten globule intermediates and the mechanism of protein unfolding.
  Proteins, 78, 2725-2737.  
19217866 A.P.Yamniuk, H.Ishida, D.Lippert, and H.J.Vogel (2009).
Thermodynamic effects of noncoded and coded methionine substitutions in calmodulin.
  Biophys J, 96, 1495-1507.  
18832607 V.P.Jaakola, M.T.Griffith, M.A.Hanson, V.Cherezov, E.Y.Chien, J.R.Lane, A.P.Ijzerman, and R.C.Stevens (2008).
The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist.
  Science, 322, 1211-1217.
PDB code: 3eml
17226832 E.Estrada (2007).
Point scattering: a new geometric invariant with applications from (nano)clusters to biomolecules.
  J Comput Chem, 28, 767-777.  
16542150 J.Font, A.Benito, J.Torrent, R.Lange, M.Ribó, and M.Vilanova (2006).
Pressure- and temperature-induced unfolding studies: thermodynamics of core hydrophobicity and packing of ribonuclease A.
  Biol Chem, 387, 285-296.  
17038664 P.Cioni (2006).
Role of protein cavities on unfolding volume change and on internal dynamics under pressure.
  Biophys J, 91, 3390-3396.  
15688434 T.Hamelryck (2005).
An amino acid has two sides: a new 2D measure provides a different view of solvent exposure.
  Proteins, 59, 38-48.  
15698573 Y.Li, Y.Huang, C.P.Swaminathan, S.J.Smith-Gill, and R.A.Mariuzza (2005).
Magnitude of the hydrophobic effect at central versus peripheral sites in protein-protein interfaces.
  Structure, 13, 297-307.
PDB codes: 1xgp 1xgq 1xgr 1xgt 1xgu
14696193 H.Zhou, and Y.Zhou (2004).
Quantifying the effect of burial of amino acid residues on protein stability.
  Proteins, 54, 315-322.  
15353599 J.K.Kamal, L.Zhao, and A.H.Zewail (2004).
Ultrafast hydration dynamics in protein unfolding: human serum albumin.
  Proc Natl Acad Sci U S A, 101, 13411-13416.  
12799387 K.Takano, J.M.Scholtz, J.C.Sacchettini, and C.N.Pace (2003).
The contribution of polar group burial to protein stability is strongly context-dependent.
  J Biol Chem, 278, 31790-31795.
PDB codes: 1uci 1ucj 1uck 1ucl
12941968 P.Saxena, G.Yadav, D.Mohanty, and R.S.Gokhale (2003).
A new family of type III polyketide synthases in Mycobacterium tuberculosis.
  J Biol Chem, 278, 44780-44790.  
12205097 A.I.Arunkumar, S.Srisailam, T.K.Kumar, K.M.Kathir, Y.H.Chi, H.M.Wang, G.G.Chang, I.Chiu, and C.Yu (2002).
Structure and stability of an acidic fibroblast growth factor from Notophthalmus viridescens.
  J Biol Chem, 277, 46424-46432.
PDB code: 1fmm
12142453 A.L.Lomize, M.Y.Reibarkh, and I.D.Pogozheva (2002).
Interatomic potentials and solvation parameters from protein engineering data for buried residues.
  Protein Sci, 11, 1984-2000.  
11959988 A.R.Viguera, C.Vega, and L.Serrano (2002).
Unspecific hydrophobic stabilization of folding transition states.
  Proc Natl Acad Sci U S A, 99, 5349-5354.
PDB code: 1hd3
12402358 H.Zhou, and Y.Zhou (2002).
Stability scale and atomic solvation parameters extracted from 1023 mutation experiments.
  Proteins, 49, 483-492.  
12070144 S.Chakravarty, A.Bhinge, and R.Varadarajan (2002).
A procedure for detection and quantitation of cavity volumes proteins. Application to measure the strength of the hydrophobic driving force in protein folding.
  J Biol Chem, 277, 31345-31353.  
12208966 S.H.Xiang, P.D.Kwong, R.Gupta, C.D.Rizzuto, D.J.Casper, R.Wyatt, L.Wang, W.A.Hendrickson, M.L.Doyle, and J.Sodroski (2002).
Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein.
  J Virol, 76, 9888-9899.  
11148023 C.N.Pace (2001).
Polar group burial contributes more to protein stability than nonpolar group burial.
  Biochemistry, 40, 310-313.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.