Mechanism of ligand binding – PDZ domain taken as example
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Dawid Dułak
Abstract
The mechanism of specific ligand binding by proteins is discussed using the PDZ domain complexing the pentapeptide. This process is critical for clustering the membrane ion channel. The traditional model based on the Beta-sheet extension by complexed pentapeptide is interpreted as a hydrophobic core extension supported by additional Beta-strand generated by complexed pentapeptide. The explanation is based on the fuzzy oil drop model applied to the crystal structure of PDZ-pentapeptide.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The work presented in this paper was financially supported by Jagiellonian University – Medical College grant system: Funder Id: 10.13039/100009045, #K/ZDS/006363 and #K/ZDS/006366.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Roche O, Kiyama R, Brooks CL 3rd. Ligand-protein database: linking protein-ligand complex structures to binding data. J Med Chem 2001;44:3592–8.10.1021/jm000467kSuche in Google Scholar PubMed
2. Gao M, Skolnick J. The distribution of ligand-binding pockets around protein-protein interfaces suggests a general mechanism for pocket formation. Proc Natl Acad Sci U S A 2012;109:3784–9.10.1073/pnas.1117768109Suche in Google Scholar PubMed
3. Konieczny L, Brylinski M, Roterman I. Gauss-function-based model of hydrophobicity density in proteins. In Silico Biol 2006;6:15–22.10.3233/ISB-00217Suche in Google Scholar PubMed
4. Dygut J, Kalinowska B, Banach M, Piwowar M, Konieczny L, Roterman I. Structural interface forms and their involvement in stabilization of multidomain proteins or protein complexes. Int J Mol Sci 2016;17:1741.10.3390/ijms17101741Suche in Google Scholar
5. Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R. Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 1996;85:1067–76.10.1016/S0092-8674(00)81307-0Suche in Google Scholar PubMed
6. 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: 1477–507.10.3390/e17031477Suche in Google Scholar
7. Banach M, Kalinowska B, Konieczny L, Roterman I. Role of disulfide bonds in stabilizing the conformation of selected enzymes – an approach based on divergence entropy applied to the structure of hydrophobic core in proteins. Entropy 2016;18:67.10.3390/e18030067Suche in Google Scholar
8. Banach M, Konieczny L, Roterman I. Ligand-binding site recognition. In: Roterman I, editor. Protein folding in silico – protein folding versus protein structure prediction. Cambridge, UK: Woodhead Publishing, 2012;79–94.10.1533/9781908818256.79Suche in Google Scholar
9. Banach M, Konieczny L, Roterman I. Use of the “fuzzy oil drop” model to identify the complexation area in protein homodimers. In: Roterman I, editor. Protein folding in silico – protein folding versus protein structure prediction. Cambridge, UK: Woodhead Publishing, 2012:95–122.10.1533/9781908818256.95Suche in Google Scholar
10. Kullback S, Leibler RA. On information and sufficiency. Ann Math Stat 1951;22:79–86.10.1214/aoms/1177729694Suche in Google Scholar
11. Konieczny L, Roterman I, Spólnik P. Systems biology. New York, Heidelberg, Dordrecht, London: Springer, 2014.10.1007/978-3-319-01336-7Suche in Google Scholar
12. Biedermann F, Nau WM, Schneider H-J. The hydrophobic effect revisited – studies with supramolecular complexes imply high-energy water as a noncovaluent driving force. Angew Chem 2014;53:11158–71.10.1002/anie.201310958Suche in Google Scholar PubMed
13. Ben-Naim A. Solvent-induced interactions: hydrophobic and hydrophilic phenomena. J Chem Phys 1989;90: 7412–525.10.1063/1.456221Suche in Google Scholar
14. Schutzius TM, Jung S, Maitra T, Graeber G, Köhme M, Poulikakos D. Spontaneous droplet trampolining on rigid superhydrophobic surfaces. Nature 2015;527:82–5.10.1038/nature15738Suche in Google Scholar PubMed
15. Banach M, Konieczny L, Roterman I. Why do antifreeze proteins require a solenoid? Biochimie 2018;144:74–84.10.1016/j.biochi.2017.10.011Suche in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
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- Mechanism of ligand binding – PDZ domain taken as example
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- Modified S-transform as a tool to identify secondary structure elements in RNA
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Artikel in diesem Heft
- Frontmatter
- Research Articles
- Mechanism of ligand binding – PDZ domain taken as example
- Chain-chain complexation and heme binding in haemoglobin with respect to the hydrophobic core structure
- Modified S-transform as a tool to identify secondary structure elements in RNA
- Electronic health record for elderly patients
- Evaluation of lexicon- and syntax-based negation detection algorithms using clinical text data
- Short Communication
- An improved structural model of the human iron exporter ferroportin. Insight into the role of pathogenic mutations in hereditary hemochromatosis type 4
