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Analysis of 3D structural differences in the IgG-binding domains based on the interresidue average-distance statistics

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Abstract

It is well-known that the IgG-binding domain from staphylococcal protein A folds into a 3α helix bundle structure, while the IgG-binding domain of streptococcal protein G forms an (α + β) structure. Recently, He et al. (Biochemistry 44:14055–14061, 2005) made mutants of these proteins from the wild types of protein A and protein G strains. These mutants are referred to as protein A219 and protein G311, and it was showed that these two mutants have different 3D structures, i.e., the 3α helix bundle structure and the (α + β) structure, respectively, despite the high sequence identity (59%). The purpose of our study was to clarify how such 3D structural differences are coded in the sequences with high homology. To address this problem, we introduce a predicted contact map constructed based on the interresidue average-distance statistics for prediction of folding properties of a protein. We refer to this map as an average distance map (ADM). Furthermore, the statistics of interresidue distances can be converted to an effective interresidue potential. We calculated the contact frequency of each residue of a protein in random conformations with this effective interresidue potential, and then we obtained values similar to ϕ values. We refer to this contact frequency of each residue as a p(μ) value. The comparison of the p(μ) values to the ϕ values for a protein suggests that p(μ) values reveal the information on the folding initiation site. Using these techniques, we try to extract the information on the difference in the 3D structures of protein A219 and protein G311 coded in their amino acid sequences in the present work. The results show that the ADM analyses and the p(μ) value analyses predict the information of folding initiation sites, which can be used to detect the 3D difference in both proteins.

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References

  • Alexander PA, Rozak DA, Orban J, Bryan PN (2005) Directed evolution of highly homologous proteins with different folds by phage display: implications for the protein folding code. Biochemistry 44:14045–14054

    Article  PubMed  CAS  Google Scholar 

  • Chou KC (2004) Review: structural bioinformatics and its impact to biomedical science. Curr Med Chem 11:2105–2134

    PubMed  CAS  Google Scholar 

  • Chou KC, Watenpaugh KD, Heinrikson RL (1999) A model of the complex between cyclin-dependent kinase 5(Cdk5) and the activation domain of neuronal Cdk5 activator. Biochem Biophys Res Commun 259:420–428

    Article  PubMed  CAS  Google Scholar 

  • Chou KC, Wei DQ, Du QS, Sirois S, Zhong WZ (2006) Review: progress in computational approach to drug development against SARS. Curr Med Chem 13:3263–3270

    Article  PubMed  CAS  Google Scholar 

  • Daggett V, Fersht AR (2000) Transition states in protein folding. In: Pain RH (ed) Mechanisms of protein folding, 2nd edn. Oxford University Press, Oxford

    Google Scholar 

  • Du QS, Wang SQ, Chou KC (2007) Analogue inhibitors by modifying oseltamivir based on the crystal neuraminidase structure for treating drug-resistant H5N1 virus. Biochem Biophys Res Commun 362:525–531

    Article  PubMed  CAS  Google Scholar 

  • Gao WN, Wei DQ, Li Y, Gao H, Xu WR, Li AX, Chou KC (2007) Agaritine and its derivatives are potential inhibitors against HIV proteases. Med Chem 3:221–226

    Article  PubMed  CAS  Google Scholar 

  • He Y, Yeh DC, Alexander P, Bryan PN (2005) Solution NMR structures of IgG binding domains with artificially evolved high levels of sequence identity but different folds. Biochemistry 44:14055–14061

    Article  PubMed  CAS  Google Scholar 

  • Ichimaru T, Kikuchi T (2003) Analysis of the differences in the folding kinetics of structurally homologous proteins based on predictions of the gross features of residue contacts. Proteins 51:515–530

    Article  PubMed  CAS  Google Scholar 

  • Kikuchi T (1996) Inter-Cα atomic potentials derived from the statistics of average interresidue distances in proteins: application to bovine pancreatic trypsin inhibitor. J Comput Chem 17:226–237

    Article  CAS  Google Scholar 

  • Kikuchi T (1999) Study of protein fluctuation with an effective inter-Cα atomic potential derived from average distances between amino acids in proteins. J Comput Chem 20:713–719

    Article  CAS  Google Scholar 

  • Kikuchi T (2002) Application to the prediction of structures and active sites of proteins and peptides. In: Pandalai SG (ed) Recent research developments in protein engineering. Research Signpost, Kerala

    Google Scholar 

  • Kikuchi T, Némethy G, Scheraga HA (1988) Prediction of the location of structural domains in globular proteins. J Protein Chem 7:427–471

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Wei DQ, Gao WN, Gao H, Liu BN, Huang CJ, Xu WR, Liu DK, Chen HF, Chou KC (2007) Computational approach to drug design for oxazolidinones as antibacterial agents. Med Chem 3:576–582

    Article  PubMed  CAS  Google Scholar 

  • Lubec G, Afjehi-Sadat L, Yang JW, John JP (2005) Searching for hypothetical proteins: theory and practice based upon original data and literature. Prog Neurobiol 77:90–127

    Article  PubMed  CAS  Google Scholar 

  • McCallinger EL, Alm E, Baker D (2000) Critical role of b-hairpin formation in protein G folding. Nat Struct Biol 7:669–673

    Article  Google Scholar 

  • Nakajima S, Emma A-S, Kikuchi T, Arredondo-Peter R (2005) Prediction of folding pathway and kinetics among plant hemoglobins using an average distance map method. Proteins 61:500–506

    Article  PubMed  CAS  Google Scholar 

  • Oxenoid K, Chou JJ (2005) The structure of phospholamban pentamer reveals a channel-like architecture in membranes. Proc Natl Acad Sci USA 102:10870–10875

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Fersht AR (2007) Searching for multiple folding pathways of a nearly symmetrical protein: temperature dependent ϕ-value analysis of the b domain of protein A. J Mol Biol 372:254–267

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Religa TL, Daggett V, Fersht AR (2004) Testing protein-folding simulations by experiment: B domain of protein A. Proc Nat Acad Sci USA 101:6952–6956

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Religa TL, Fersht AR (2006) ϕ-analysis of the folding of the B domain of protein a using multiple optical probes. J Mol Biol 360:850–864

    Article  PubMed  CAS  Google Scholar 

  • Schnell JR, Chou JJ (2008) Structure and mechanism of the M2 proton channel of influenza A virus. Nature 451:591–595

    Article  PubMed  CAS  Google Scholar 

  • Scott KA, Dagget V (2007) Folding mechanisms of proteins with high sequence identity but different folds. Biochemistry 46:1545–1556

    Article  PubMed  CAS  Google Scholar 

  • Wang SQ, Du QS, Chou KC (2007a) Study of drug resistance of chicken influenza A virus (H5N1) from homology-modeled 3D structures of neuraminidases. Biochem Biophys Res Commun 354:634–640

    Article  PubMed  CAS  Google Scholar 

  • Wang SQ, Du QS, Zhao K, Li AX, Wei DQ, Chou KC (2007b) Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy. Amino Acids 33:129–135

    Article  PubMed  Google Scholar 

  • Wei DQ, Du QS, Sun H, Chou KC (2006a) Insights from modeling the 3D structure of H5N1 influenza virus neuraminidase and its binding interactions with ligands. Biochem Biophys Res Comm 344:1048–1055

    Article  PubMed  CAS  Google Scholar 

  • Wei DQ, Zhang R, Du QS, Gao WN, Li Y, Gao H, Wang SQ, Zhang X, Li AX, Sirois S, Chou KC (2006b) Anti-SARS drug screening by molecular docking. Amino Acids 31:73–80

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Yan S (2008) Prediction of mutations engineered by randomness in H5N1 neuraminidases from influenza A virus. Amino Acids 34:81–90

    Article  PubMed  CAS  Google Scholar 

  • Ye Y, Wei J, Dai X, Gao Q (2007) Computational studies of the binding modes of A2A adenosine receptor antagonists. Amino Acids. doi:10.1007/s00726-007-0604-2

  • Zhang R, Wei DQ, Du QS, Chou KC (2006) Molecular modeling studies of peptide drug candidates against SARS. Med Chem 2:309–314

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Grant-in-Aids for Scientific Research (C) (no. 19510202) from the Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan.

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Correspondence to Takeshi Kikuchi.

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Kikuchi, T. Analysis of 3D structural differences in the IgG-binding domains based on the interresidue average-distance statistics. Amino Acids 35, 541–549 (2008). https://doi.org/10.1007/s00726-008-0082-1

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