Label-free affinity screening, design and synthesis of inhibitors targeting the Mycobacterium tuberculosis L-alanine dehydrogenase
Fig 4
AlaDH crystal structure in complex with adenosine-based inhibitors.
(a) N6-isobutyl adenosine inhibitor binding site showing hydrophobic interactions and hydrogen bonds. Electron density is shown as polder omit map at 3σ [48]. (b) Crystallographic structure bound to N6-isobutyl adenosine and (c) N6-methyl adenosine. Dashed lines show closest interatomic distances between the N6-methyl or N6-isobutyl moieties to surrounding hydrophobic residues. It can be seen that each distance for the N6-methyl moiety is longer than the corresponding nearest distance to the N6-isobutyl moiety (6.6 vs. 4.4 Å for A222; 4.1 vs. 4.0 Å for L225, 3.9 vs. 3.6 Å for L249; 4.4 vs. 3.9 Å for I199).