Structural basis of binding of high-affinity ligands to protein kinase C: Prediction of the binding modes through a new molecular dynamics method and evaluation by site-directed mutagenesis

Journal of Medicinal Chemistry

Volumn 44, Issue 11, 2001, Pages 1690-1701

  Pak, Y ^a,b   Enyedy, I J ^a   Varady, J ^a   Kung, J W ^c   Lorenzo, P S ^c   Blumberg, P M ^c   Wang, S ^a  

^a GEORGETOWN UNIVERSITY   (United States)

^b Pusan National University   (South Korea)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INDOLACTAM V; INGENOL 3 BENZOATE; LIGAND; PHORBOL DIBUTYRATE; PROTEIN KINASE C; THYMELEATOXIN; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; BINDING SITE; CONFORMATIONAL TRANSITION; GENE MUTATION; HYDROGEN BOND; HYDROPHOBICITY; LIGAND BINDING; MOLECULAR DYNAMICS; SIMULATION; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; SYSTEM ANALYSIS; X RAY ANALYSIS;

CRYSTALLOGRAPHY, X-RAY; INDOLES; ISOENZYMES; LACTAMS; LIGANDS; MODELS, MOLECULAR; MONTE CARLO METHOD; MUTAGENESIS, SITE-DIRECTED; PHORBOL 12,13-DIBUTYRATE; PHORBOL ESTERS; PROTEIN BINDING; PROTEIN KINASE C; PROTEIN KINASE C-DELTA;

EID: 0035942521     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm000488e     Document Type: Article

References (39)

1. The role of protein kinase C in cell surface signal transduction and tumor promotion
2. Studies and perspectives of protein kinase C
3. The molecular heterogeneity of protein kinase C and its implications for cellular recognition
4. Characterization of ligand and substrate specificity for the calcium-dependent and calcium-independent PKC isozymes
5. Comparison of the activity of phorbol 12-myristate 13-acetate and the diglyceride glycerol 1-myristate 2-acetate
6. Protein kinase C as the receptor for the phorbol ester tumor promoters. Sixth Rhoads Memorial award lecture
7. Protein kinase C contains two phorbol ester binding domains
8. A phorbol ester binding domain of protein kinase C gamma. High affinity binding to a glutathione-S-transferase/Cys2 fusion protein
9. 3H]bryostatin 1 and analogs to calcium-dependent and calcium-independent PKC isozymes
10. Crystal structure of the cys2 activator-binding domain of protein kinase C in complex with phorbol ester
11. Computer-assisted molecular modeling of tumor promoters: Rationale for the activity of phorbol esters, teleocidin B and aplysiatoxin
12. Analysis of the phorbol ester pharmacophore on protein kinase C as a guide to the rational design of new classes of analogs
13. A receptor model for tumor promoters: Rational superposition of teleocidins and phorbol esters
14. Modeling of the bryostatins to the phorbol ester pharmacophore on protein kinase C
15. Structural basis of protein kinase C activation by tumor promoters
16. The pharmacophore of debromoaplysiatoxin responsible for protein kinase C activation
17. Structural basis of protein kinase C activation by diacylglycerols and tumor promoters
18. Probing the binding of indolactam-V to protein kinase C through site-directed mutagenesis and computational docking simulations
19. Folding of a 16-residue helical peptide using molecular dynamics simulation with Tsallis effective potential
20. Application of a molecular dynamics simulation method with a generalized effective potential to the flexible molecular docking problems
21. Possible generalization of Boltzmann-Gibbs statistics
22. Generalized statistical mechanics: Connection with thermodynamics
23. Generalized simulated annealing algorithms using Tsallis statistics: Application to conformational optimization of a tetrapeptide
24. On Monte Carlo and molecular dynamics methods inspired by Tsallis statistics: Methodology, optimization, and application to atomic cluster
25. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations
26. All-atom empirical potential for molecular modeling and dynamics studies of proteins
27. Synthesis and biological activities of new conformationally restricted analogues of (-)-indolactam-V: Elucidation of the biologically active conformation of the tumor-promoting teleocidins
28. Modeling, chemistry, and biology of the benzolactam analogues of ILV. 2. Identification of the binding site of the benzolactams in the CRD2 activator-binding domain of PKC δ and discovery of an ILV analogue of improved isozyme selectivity
29. Molecular dynamics with coupling to an external bath
30. Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of N-alkanes
31. Residues in the second cysteine-rich region of PKC relevant to phorbol ester binding as revealed by site-directed mutagenesis
32. Conformationally constrained analogues of diacylglycerol. Ultrapotent protein kinase C (PK-C) ligands based on a racemic 5-disubstituted tetrahydro-2-furanone
33. Conformationally constrained analogues of diacylglycerol. Ultrapotent protein kinase C (PK-C) ligands based on a chiral 5-(acyloxymethyl)-5-(hydroxymethyl)tetrahydro-2-furanone template
34. Conformationally constrained analogues of diacylglycerol. Ultrapotent protein kinase C (PK-C) ligands based on a chiral 4-disubstituted heptono-1,4-lactone template
35. The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1
36. The discovery of novel, structurally diverse PK-C agonists through computer 3D-database pharmacophore search. Molecular modeling studies
37. Structure-based design of a novel class, high affinity protein kinase C ligands