Exhaustive de novo Design of Low-Molecular-Weight Fragments Against the ATP-Binding Site of DNA-Gyrase

2006 ◽  
Vol 46 (3) ◽  
pp. 1168-1173 ◽  
Author(s):  
Stuart Firth-Clark ◽  
Nikolay P. Todorov ◽  
Ian L. Alberts ◽  
Anthony Williams ◽  
Timothy James ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Binding Site ◽  
De Novo ◽  
Dna Gyrase ◽  
De Novo Design ◽  
Low Molecular Weight ◽  
Atp Binding ◽  
Atp Binding Site

Exhaustive ne novo Design of Low-Molecular-Weight Fragments Against the ATP-Binding Site of DNA-Gyrase.

ChemInform ◽  
2006 ◽  
Vol 37 (30) ◽  
Author(s):  
Stuart Firth-Clark ◽  
Nikolay P. Todorov ◽  
Ian L. Alberts ◽  
Anthony Williams ◽  
Timothy James ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Binding Site ◽  
Dna Gyrase ◽  
Low Molecular Weight ◽  
Atp Binding ◽  
Atp Binding Site

Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site

2015 ◽  
Vol 58 (14) ◽  
pp. 5501-5521 ◽  
Author(s):  
Tihomir Tomašič ◽  
Sotirios Katsamakas ◽  
Žiga Hodnik ◽  
Janez Ilaš ◽  
Matjaž Brvar ◽  
...  
Keyword(s):  
Binding Site ◽  
Dna Gyrase ◽  
Atp Binding ◽  
Atp Binding Site ◽  
Gyrase Inhibitors

Biophysical characterization of an indolinone inhibitor in the ATP-binding site of DNA gyrase

2006 ◽  
Vol 349 (4) ◽  
pp. 1206-1213 ◽  
Author(s):  
Marko Oblak ◽  
Simona Golič Grdadolnik ◽  
Miha Kotnik ◽  
Arnaud Poterszman ◽  
R. Andrew Atkinson ◽  
...  
Keyword(s):  
Binding Site ◽  
Dna Gyrase ◽  
Atp Binding ◽  
Biophysical Characterization ◽  
Atp Binding Site

Green Tea Catechins Inhibit Bacterial DNA Gyrase by Interaction with Its ATP Binding Site

2007 ◽  
Vol 50 (2) ◽  
pp. 264-271 ◽  
Author(s):  
Helena Gradišar ◽  
Primož Pristovšek ◽  
Andreja Plaper ◽  
Roman Jerala
Keyword(s):  
Binding Site ◽  
Green Tea ◽  
Dna Gyrase ◽  
Atp Binding ◽  
Tea Catechins ◽  
Bacterial Dna ◽  
Atp Binding Site ◽  
Green Tea Catechins

Linker-switch approach towards new ATP binding site inhibitors of DNA gyrase B

2017 ◽  
Vol 125 ◽  
pp. 500-514 ◽  
Author(s):  
Marko Jukič ◽  
Janez Ilaš ◽  
Matjaž Brvar ◽  
Danijel Kikelj ◽  
Jožko Cesar ◽  
...  
Keyword(s):  
Binding Site ◽  
Dna Gyrase ◽  
Atp Binding ◽  
Atp Binding Site

scholarly journals The ATP binding site of the chromatin remodeling homolog Lsh is required for nucleosome density and de novo DNA methylation at repeat sequences

2015 ◽  
Vol 43 (3) ◽  
pp. 1444-1455 ◽  
Author(s):  
Jianke Ren ◽  
Victorino Briones ◽  
Samantha Barbour ◽  
Weishi Yu ◽  
Yixing Han ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Binding Site ◽  
Chromatin Remodeling ◽  
De Novo ◽  
Atp Binding ◽  
Atp Binding Site ◽  
Repeat Sequences ◽  
Nucleosome Density

Functionality Maps of the ATP Binding Site of DNA Gyrase B:  Generation of a Consensus Model of Ligand Binding

2004 ◽  
Vol 47 (18) ◽  
pp. 4373-4390 ◽  
Author(s):  
Martina Schechner ◽  
Finton Sirockin ◽  
Roland H. Stote ◽  
Annick P. Dejaegere
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Dna Gyrase ◽  
Atp Binding ◽  
Consensus Model ◽  
Atp Binding Site

New Mechanistic Insight on the PIM-1 Kinase Inhibitor AZD1208 Using Multidrug Resistant Human Erythroleukemia Cell Lines and Molecular Docking Simulations

2019 ◽  
Vol 19 (11) ◽  
pp. 914-926 ◽  
Author(s):  
Maiara Bernardes Marques ◽  
Michael González-Durruthy ◽  
Bruna Félix da Silva Nornberg ◽  
Bruno Rodrigues Oliveira ◽  
Daniela Volcan Almeida ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Cell Lines ◽  
Chemotherapeutic Agents ◽  
Atp Binding ◽  
Human Leukemia ◽  
Atp Binding Site ◽  
Mechanistic Insight ◽  
Multiple Drugs

Background:PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype.Objective:In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR).Materials and Methods:In order to verify a potential cytotoxic effect based on pharmacological synergism, two MDR cell lines were used: Lucena (resistant to VCR) and FEPS (resistant to DNR), both derived from the K562 non-MDR cell line, by MTT analyses. The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123. Furthermore, we performed a molecular docking simulation to delve into the molecular mechanism of PIM-1 alone, and combined with chemotherapeutic agents (VCR and DNR).Results:Our in vitro results have shown that AZD1208 alone decreases cell viability of MDR cells. However, co-exposure of AZD1208 and DNR or VCR reverses this effect. When we analyzed the ABCB1 activity AZD1208 alone was not able to affect the pump extrusion. Differently, co-exposure of AZD1208 and DNR or VCR impaired ABCB1 activity, which could be explained by compensatory expression of abcb1 or other extrusion pumps not analyzed here. Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments.Conclusion:Finally, the current results could have a pre-clinical relevance potential in the rational polypharmacology strategies to prevent multiple-drugs resistance in human leukemia cancer therapy.

scholarly journals Identification of the ATP binding site in tyrocidine synthetase 1 by selective modification with fluorescein 5'-isothiocyanate.

1994 ◽  
Vol 269 (21) ◽  
pp. 14962-14966
Author(s):  
M. Pavela-Vrancic ◽  
E. Pfeifer ◽  
W. Schröder ◽  
H. von Döhren ◽  
H. Kleinkauf
Keyword(s):  
Binding Site ◽  
Atp Binding ◽  
Atp Binding Site
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