Premium
Determination of the Bound Conformation of a Competitive Nanomolar Inhibitor of Mycobacterium tuberculosis Type II Dehydroquinase by NMR Spectroscopy
Author(s) -
Prazeres Verónica F. V.,
SánchezSixto Cristina,
Castedo Luis,
Canales Ángeles,
Cañada Francisco Javier,
JiménezBarbero Jesús,
Lamb Heather,
Hawkins Alastair R.,
GonzálezBello Concepción
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200600100
Subject(s) - mycobacterium tuberculosis , stereochemistry , chemistry , context (archaeology) , two dimensional nuclear magnetic resonance spectroscopy , nuclear magnetic resonance spectroscopy , tuberculosis , biology , medicine , paleontology , pathology
The synergy between tuberculosis and the AIDS epidemic, along with the surge of multidrug‐resistant isolates of M. tuberculosis , has reaffirmed tuberculosis as a primary public health threat. It is therefore necessary to discover new, safe, and more efficient antibiotics against this disease. On the other hand, mapping the dynamic interactions of inhibitors of a target protein can provide information for the development of more potent inhibitors and consequently, more potent potential drugs. In this context, the conformational binding of our previously reported nanomolar inhibitor of M. tuberculosis type II dehydroquinase, the 3‐nitrophenyl derivative 1 , was studied using saturation transfer difference (STD) and transferred NOESY experiments. These studies have shown that in the bound state, one conformation of those present in solution of the competitive nanomolar inhibitor 3‐nitrophenyl derivative 1 is selected. In the bound conformation, the aromatic ring is slightly shifted from coplanarity, with the double bond and the nitro group of 1 oriented towards the double bond side.