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![[Figure 6]](en5210fig6mag.jpg)
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Figure 6
(a) Stereoview of the complexes of ENR from P. falciparum (red), B. napus (magenta) and E. coli (green) with NAD+ and triclosan and of M. tuberculosis ENR in complex with NAD+ (yellow) and with NAD+ and C-16 fatty-acid substrate, labelled C-16 (blue). In addition to ENR, the catalytic Lys and Tyr residues of the 3β/17β-hydroxysteroid dehydrogenase SDR enzyme are shown (orange). The positions of two apparently conserved water molecules in the active site of each of these enzymes are shown as coloured spheres. The water molecules in ENR form interactions with several active-site residues, including the catalytic lysine and the 3′-OH of the NAD+ nicotinamide ribose. (b) Stereoview of the differences in position for the substrate-binding helix (α6 or α7 in the bacterial and plant/parasite ENRs, respectively) upon the binding of different inhibitors to EcENR. The loop region which moves upon inhibitor binding and the corresponding inhibitor in the EcENR complex is coloured cream, green, red and blue for benzo-diazaborine, triclosan, compound 29 and imidazole, respectively. For clarity, only those residues which make direct interactions with the inhibitors in one or more complexes are shown in stick representation and numbered. (c) Close-up of the E. coli ENR–NAD+–compound 29 complex (red), E. coli ENR–NAD+–triclosan complex (green) and T. gondii ENR–NAD+–triclosan complex (yellow) superimposed, with critical residues involved in inhibitor binding shown in stick representation with the TgENR structure numbered. Modelling of compound 29 into the structure of TgENR in complex with NAD+ (black) and triclosan shows that a severe steric clash might occur owing to the difference in the structure close to Phe242, which in EcENR is replaced by Asp202. (d) Representation of the van der Waals surfaces of the protein (coloured red) within the active site of E. coli, T. gondii and P. falciparum ENR close to the phenolic ring of triclosan (blue). Both the P. falciprum and T. gondii ENRs appear to be less closely packed with triclosan owing to the presence of an alanine residue at the base of the binding pocket in contrast to the bulkier methionine residue in the E. coli enzyme. |
![[Figure 6]](en5210fig6.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
