Hydrophobic core structure of macromomycin – the apoprotein of the antitumor antibiotic auromomycin – fuzzy oil drop model applied
Wybrane pełne teksty z tego czasopisma
The fuzzy oil drop model was applied to analyze the structure of macromomycin, the apoprotein of the antitumor antibiotic auromomycin, revealing the differentiation of β-structural fragments present in β-sandwich. The seven-stranded antiparallel β-barrel and two antiparallel β-sheet ribbons represent the highly ordered geometry of the structure. However, participation in hydrophobic core formation appears different. The structure of the complete domain represents the status of the irregular hydrophobic core; however, some β-structural fragments appear to represent the hydrophobicity density distribution accordant with the idealized distribution of hydrophobicity as expected using the fuzzy oil drop model. Four β-structural fragments generating one common layer appear to be unstable in respect to the general structure of the hydrophobic core. This area is expected to be more flexible than other parts of the molecule. The protein binds the ligand – chromophore, two 2-methyl-2,4-pentanediol – in a well- defined cleft. The presence of this cleft makes the general structure of the hydrophobic core irregular (as it may be interpreted using the fuzzy oil drop model). Two short loops generated by two SS bonds fit very well to the general distribution of hydrophobicity density as expected for the model. No information about the potential amyloidogenic character of this protein is given in the literature; however, the specificity of the hydrophobicity distribution profile is found to be highly similar to the one observed in transthyretin (Banach M, Konieczny L, Roterman I. The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function. J Theor Biol 2014;359:6–17), suggesting a possible tendency to turn to the amyloid form. A detailed analysis of macromomycin will be given, and a comparable analysis with other proteins of β-sandwich or β-barrel will be presented.
Bibliogr. 18 poz., rys., tab.
- 1. Banach M, Konieczny L, Roterman I. The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function. J Theor Biol 2014;359:6–17.
- 2. Kalinowska B, Banach M, Konieczny L, Roterman I. Application of divergence entropy to characterize the structure of the hydrophobic core in DNA interacting proteins. Entropy 2015;17: 1477–507.
- 3. Van Roey P, Beerman TA. Crystal structure analysis of auromomycin apoprotein (macromomycin) shows importance of protein side chains to chromophore binding selectivity. Proc Natl Acad Sci USA 1989;86:6587–91.
- 4. Banach M, Prymula K, Jurkowski W, Konieczny L. Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants. J Mol Mod 2012;18:229–37.
- 5. Roterman I, Konieczny L, Jurkowski W, Prymula K, Banach M. Two-intermediate model to characterize the structure of fastfolding proteins. J Theor Biol 2011;283:60–70.
- 6. Banach M, Konieczny L, Roterman I. Can the structure of hydrophobic core determine the complexation site? In: Roterman-Konieczna I, editor. Identification of ligand binding site and protein-protein interaction area. Dordrecht: Springer, 2013: 41–54.
- 7. Banach M, Konieczny L, Roterman I. Use of the “fuzzy oil drop” model to identify the complexation area in protein homodimers. In: Roterman-Konieczna I, editor. Protein folding in silico. Oxford: Woodhead Publishing, 2012:95–122.
- 8. Prymula K, Jadczyk T, Roterman I. Catalytic residues in hydrolases: analysis of methods designer for ligand-binding site in proteins J Comp Aid Mol Des 2011;25:117–33.
- 9. Kalinowska B, Banach M, Konieczny L, Marchewka D, Roterman I. Intrinsically disordered proteins-relation to general model expressing the active role of the water environment. Adv Protein Chem Struct Biol 2014;94:315–46.
- 10. Kalinowska B, Banach M, Konieczny L, Roterman I. Divergence entropy to characterise the structure of hydrophobic core in proteins. Entropy 2015;17:1477–507.
- 11. Banach M, Prudhomme N, Carpentier M, Duprat E, Papandreou N, Kalinowska B, et al. Contribution to the prediction of the fold code: application to immunoglobulin and flavodoxin cases. PLoS One 2015;10:e0125098.
- 12. Roterman-Konieczna I, editor. Protein folding in silico: protein folding versus protein structure prediction. Oxford: Woodhead Publishing (currently Elsevier), 2012.
- 13. Levitt MA. A simplified representation of protein conformations for rapid simulation of protein holding. J Mol Biol 1976;104: 59–107.
- 14. Kullback S, Leibler RA. On information and sufficiency. Ann Math Stat 1951;22:79–86.
- 15. Banach M, Konieczny L, Roterman I. Ligand binding site recognition. In: Roterman-Konieczna I, editor. Protein folding in silico. Oxford: Woodhead Publishing, 2012:78–94.
- 16. Laskowski RA. Enhancing the functional annotation of PDB structures in PDBsum using key figures extracted from the literature. Bioinformatics 2007;23:1824–7.
- 17. Das P, Kapoor D, Halloran KT, Zhou R, Matthews CR. Interplay between drying and stability of a TIM barrel protein: a combined simulation-experimental study. J Am Chem Soc 2013;135:1882–90.
- 18. Galzitskaya OV, Ivankov DN, Finkelstein AV. Folding nuclei in proteins. FEBS Lett 2001;489:113–8.