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

2001 ◽  
Vol 44 (11) ◽  
pp. 1690-1701 ◽  
Author(s):  
Youngshang Pak ◽  
Istvan J. Enyedy ◽  
Judith Varady ◽  
Justin W. Kung ◽  
Patricia S. Lorenzo ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Protein Kinase C ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Directed Mutagenesis ◽  
Binding Modes ◽  
Affinity Ligands ◽  
High Affinity ◽  
Kinase C ◽  
Dynamics Method

scholarly journals Residues in the Second Cysteine-rich Region of Protein Kinase C δ Relevant to Phorbol Ester Binding as Revealed by Site-directed Mutagenesis

1995 ◽  
Vol 270 (37) ◽  
pp. 21852-21859 ◽  
Author(s):  
Marcelo G. Kazanietz ◽  
Shaomeng Wang ◽  
George W. A. Milne ◽  
Nancy E. Lewin ◽  
Howard L. Liu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Rich Region ◽  
Kinase C

Probing the Binding of Indolactam-V to Protein Kinase C through Site-Directed Mutagenesis and Computational Docking Simulations

1999 ◽  
Vol 42 (18) ◽  
pp. 3436-3446 ◽  
Author(s):  
Shaomeng Wang ◽  
Ming Liu ◽  
Nancy E. Lewin ◽  
Patricia S. Lorenzo ◽  
Dipak Bhattacharrya ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Computational Docking ◽  
Docking Simulations ◽  
Kinase C

Molecular Modeling and Site-Directed Mutagenesis Studies of a Phorbol Ester-Binding Site in Protein Kinase C

1996 ◽  
Vol 39 (13) ◽  
pp. 2541-2553 ◽  
Author(s):  
Shaomeng Wang ◽  
Marcelo G. Kazanietz ◽  
Peter M. Blumberg ◽  
Victor E. Marquez ◽  
G. W. A. Milne
Keyword(s):  
Protein Kinase C ◽  
Molecular Modeling ◽  
Protein Kinase ◽  
Binding Site ◽  
Phorbol Ester ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Kinase C

scholarly journals Analysis of Gz alpha by site-directed mutagenesis. Sites and specificity of protein kinase C-dependent phosphorylation.

1993 ◽  
Vol 268 (5) ◽  
pp. 3494-3498
Author(s):  
K.M. Lounsbury ◽  
B. Schlegel ◽  
M. Poncz ◽  
L.F. Brass ◽  
D.R. Manning
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Kinase C

Probing the Interaction between a High-Affinity Single-Chain Fv and a Pyrimidine (6-4) Pyrimidone Photodimer by Site-Directed Mutagenesis†

Biochemistry ◽  
1999 ◽  
Vol 38 (2) ◽  
pp. 532-539 ◽  
Author(s):  
Hiroyuki Kobayashi ◽  
Hiroshi Morioka ◽  
Kunihiro Tobisawa ◽  
Takuya Torizawa ◽  
Koichi Kato ◽  
...  
Keyword(s):  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Single Chain ◽  
High Affinity ◽  
Single Chain Fv

scholarly journals Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhiwen Liu ◽  
Fanglong Zhao ◽  
Boyang Zhao ◽  
Jie Yang ◽  
Joseph Ferrara ◽  
...  
Keyword(s):  
High Resolution ◽  
Organic Synthesis ◽  
Indole Alkaloids ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Directed Mutagenesis ◽  
Computational Studies ◽  
X Ray ◽  
Evolutionary Branch ◽  
Catalytic Mechanisms

AbstractPrenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible β-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.

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