Targeting human DNA polymerase a for the inhibition of keratinocyte proliferation. Part 1. Homology model, active site architecture and ligand binding

Journal of Enzyme Inhibition and Medicinal Chemistry

Volumn 23, Issue 1, 2008, Pages 94-100

  Richartz, Anja ^a   Höltje, Monika ^b   Brandt, Birte ^b   Schäfer Korting, Monika ^a   Höltje, Hans Dieter ^b  

^a FREIE UNIVERSITÄT BERLIN   (Germany)

^b HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

Aphidicolin; DNA polymerase ; Homology model; Molecular modelling

Indexed keywords

2 BUTYLANILINODEOXYADENOSINE TRIPHOSPHATE; 2',3' DIDEOXYNUCLEOTIDE DERIVATIVE; ADEFOVIR; APHIDICOLIN; DNA DIRECTED DNA POLYMERASE ALPHA; DNA DIRECTED DNA POLYMERASE ALPHA INHIBITOR; ENZYME INHIBITOR; LAMIVUDINE; NUCLEOTIDE DERIVATIVE; STAVUDINE; TENOFOVIR; UNCLASSIFIED DRUG; ZIDOVUDINE;

ARTICLE; CATALYSIS; CELL PROLIFERATION; COMPUTER SIMULATION; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG RESEARCH; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME INHIBITION; ENZYME STABILITY; KERATINOCYTE; LIGAND BINDING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR MODEL; PRIORITY JOURNAL; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION;

ADENINE; ANTIVIRAL AGENTS; APHIDICOLIN; BINDING SITES; CELL DIVISION; DNA POLYMERASE I; ENZYME INHIBITORS; HUMANS; KERATINOCYTES; LIGANDS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; PHOSPHONIC ACIDS; PROTEIN CONFORMATION; REVERSE TRANSCRIPTASE INHIBITORS;

EID: 39349108168     PISSN: 14756366     EISSN: 14756374     Source Type: Journal    
DOI: 10.1080/14756360701433414     Document Type: Article

References (20)

1. Chakrabaty, A. and Geisse, JK (2004) Medical therapies for non-melanoma skin cancer. Clin Dermatol, 22, pp. 183-188.
2. Alba, M. (2001) Replicative DNA polymerises. Genome Biol, 2
3. Steitz, TA (1999) DNA polymerases: Structural diversity and common mechanisms. J Biol Chem, 274, pp. 17395-17398.
4. Thompson, JD, Higgins, DG and Gibson, TJ (1994) CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res, 22, pp. 4673-4680.
5. Altschul, SF, Madden, TL, Schaffer, AA, Zhang, J., Zhang, Z., Miller, W. and Lipman, DJ (1997) Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res, 25, pp. 3389-3402.
6. Jones, DT (1999) Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol, 292, pp. 195-202.
7. Franklin, MC, Wang, J. and Steitz, TA (2001) Structure of the replicating complex of a pol alpha family DNA polymerase. Cell, 105, pp. 657-667.
8. Laskowski, R., MacArthur, M., Moss, D. and Thornton, J. (1993) (1993) PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Cryst, 26, pp. 283-291.
9. (2003) Introduction to Comparative Protein Modeling. Molecular modeling: Basic principles and applications, pp. 87-142. Wiley-VCH Verlag, Weinheim
10. Rupp, B., Raub, S., Marian, C. and Höltje, HD (2005) Molecular design of 2 sterol-14 a-demethylase homology models and their interactions with the azole antifungals ketoconazole and bifonazole. J Comput Aided Mol Des, 19, pp. 149-163.
11. Lindahl, E., Hess, B. and van der Spoel, D. (2001) GROMACS 3.0: A package for molecular simulation and trajectory analysis. J Mol Model, 7, pp. 306-317.
12. Cihlar, T. and Chen, M. (1997) Incorporation of selected nucleoside phosphonates and anti-human immunodeficiency virus nucleotide analogues into DNA by human DNA polymerases α, β, and γ. Antivir Chem Chemother, 8, pp. 187-195.
13. Khan, NN, Wright, GE, Dudycz, LW and Brown, NC (1984) Butylphenyl dGTP: A selective and potent inhibitor of mammalian DNA polymerase alpha. Nucleic Acids Res, 12, pp. 3695-3706.
14. Arabshahi, L., Brown, N., Khan, N. and Wright, G. (1988) Inhibition of DNA polymerase alpha by aphidicolin derivatives. Nucleic Acids Res, 16, pp. 5107-5113.
15. Selmi, B., Boretto, J., Sarfati, SR, Guerreiro, C. and Canard, B. (2001) Mechanism-based suppression of dideoxynucleotide resistance by K65R human immunodeficiency virus reverse transcriptase using an alpha-boranophosphate nucleoside analogue. J Biol Chem, 276, pp. 48466-48472.
16. Yang, G., Franklin, M., Li, J., Lin, TC and Konigsberg, W. (2002) A conserved Tyr residue is required for sugar selectivity in a pol alpha DNA polymerase. Biochemistry, 41, pp. 10256-10261.
17. Hall, JD, Wang, YS, Pierpont, J., Berlin, MS, Rundlett, SE and Woodward, S. (1989) Aphidicolin resistance in herpes simplex virus type I reveals features of the DNA polymerase dNTP binding site. Nucleic Acids Res, 17, pp. 9231-9244.
18. Copeland, WC and Wang, TS (1993) Mutational analysis of the human DNA polymerase alpha. The most conserved region in alpha-like DNA polymerases is involved in metal-specific catalysis. J Biol Chem, 268, pp. 11028-11040.
19. Esnouf, R., Ren, J., Ross, C., Jones, Y., Stammers, D. and Stuart, D. (1995) Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors. Nat Struct Biol, 2, pp. 303-308.
20. Love, RA, Parge, HE, Yu, X., Hickey, MJ, Diehl, W., Gao, J., Wriggers, H., Ekker, A., Wang, L., Thomson, JA, Dragovich, PS and Fuhrman, SA (2003) Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme. J Virol, 77, pp. 7575-7581.