Active site acidic residues and structural analysis of modelled human aromatase: A potential drug target for breast cancer

2006 ◽  
Vol 19 (12) ◽  
pp. 857-870 ◽  
Author(s):  
J. Narashima Murthy ◽  
M. Nagaraju ◽  
G. Madhavi Sastry ◽  
A. Raghuram Rao ◽  
G.␣Narahari Sastry
Keyword(s):  
Breast Cancer ◽  
Structural Analysis ◽  
Active Site ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Acidic Residues ◽  
Human Aromatase

scholarly journals Chemical validation of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase using fragment linking and CRISPR interference

2020 ◽  
Author(s):  
Jamal El Bakali ◽  
Michal Blaszczyk ◽  
Joanna C. Evans ◽  
Jennifer A. Boland ◽  
William J. McCarthy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Crystal Structures ◽  
Active Site ◽  
Drug Target ◽  
Potential Drug Target ◽  
Biosynthesis Pathway ◽  
Potential Drug ◽  
Antimicrobial Drugs ◽  
X Ray ◽  
Crispr Interference

AbstractThe coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including for the treatment of tuberculosis (TB), the lethal disease caused by Mycobacterium tuberculosis (Mtb). Seeking to identify the first inhibitors of Mtb phosphopantetheine adenylyltransferase (MtbPPAT), the enzyme that catalyses the penultimate step in CoA biosynthesis, we performed a fragment screen. In doing so, we discovered three series of fragments that occupy distinct regions of the MtbPPAT active site, presenting a unique opportunity for fragment linking. Here we show how, guided by X-ray crystal structures, we could link weakly-binding fragments to produce an active site binder with a KD < 20 μM and on-target anti-Mtb activity, as demonstrated using CRISPR interference. This study represents a big step toward validating MtbPPAT as a potential drug target and designing a MtbPPAT-targeting anti-TB drug.Abstract Figure

The Prokaryotic FAD Synthetase Family: A Potential Drug Target

2013 ◽  
Vol 19 (14) ◽  
pp. 2637-2648 ◽  
Author(s):  
Ana Serrano ◽  
Patricia Ferreira ◽  
Marta Martinez-Julvez ◽  
Milagros Medina
Keyword(s):  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug
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