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![[Figure 7]](mn5083fig7_combined_mag.jpg)
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Figure 7
BADH enzymes. (a) Conservation of residues among SaBADH (UniProtKB entry Q5HCU0), the human mitochondrial ALDH (UniProtKB entry P05091; PDB entry 1cw3; Ni et al., 1999  ), EcBADH (UniProtKB entry P77674; PDB entry 1wnb; Gruez et al., 2004), PaBADH (UniProtKB entry Q9HTJ1; PDB entry 2wme; González-Segura et al., 2009), SoBADH (UniProtKB entry P17202; PDB entry 4a0m; Díaz-Sánchez et al., 2012), AtBADH (UniProtKB entry Q8UH56; PDB entry 3r31; New York Structural Genomics Research Consortium, unpublished work) and GmBADH (UniProtKB entry P56533; PDB entry 1bpw; Johansson et al., 1998). Residues are colored from blue (variable) to red (100% conserved) and the SaBADH structure is displayed. (b) NAD+ binding imposes structural changes on the substrate-binding site, creating a solvent-accessible channel between the NAD-binding and substrate-binding sites [surface representations (the C atoms) colored as in Fig. 5c]. The large insets show whether the channel is open or closed. A solvent-accessible pocket (white `HOH'; composed of residues Gly257–Pro261, Gly281–Arg294 and Ile386–Thr397) may serve as a `buffer' for the additional structural changes required for substrate binding. The small insets show whether the channel is open (O) or closed (C) at the substrate-binding site. Val288 (gray), Tyr158 (blue) and Tyr450 (red) may determine the size of the opening, which depends on the presence/absence of NAD+ and/or a small molecule, i.e. a substrate. (c) Local structural features/changes that may favor binding of the 2′-P group of NADP+ in PaBADH (light green) and impede binding in SaBADH [NAD–SaBADHBME(+), yellow; NAD–SaBADHBME(−), light gray]. The presence of Ile28 (SaBADH) instead of the equivalent Thr26 (PaBADH) may change the coordination geometry of a metal (shown as spheres; K+1493, light green, PaBADH; Na+/K+, light gray, SaBADH; see Figs. 6d and 6e) and thus possibly affect the lower affinity of SaBADH for NADP+. (d) Merged model based on multiple structural superposition showing NAD+ and Cys289 from NAD–G234S-SaBADHBME(−) and residues Val288 (gray), Try158 (blue) and Tyr450 (red) from apo SaBADHBME(+)PEG and betaine aldehyde (BA; carbon, yellow; nitrogen, blue; oxygen, red) from human mitochondrial ALDH. |
![[Figure 7]](mn5083fig7_combined.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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