4mpb

1.7 Angstrom resolution crystal structure of betaine aldehyde dehydrogenase (betB) from Staphylococcus aureus

spinqualitylabelsall models 4mpb, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mpb is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus COL. This structure supersedes the now removed PDB entry 3ed6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, CME, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0H2X0S3_STAAC Publication Abstract from PubMed Inhibition of enzyme activity by high concentrations of substrate and/or cofactor is a general phenomenon demonstrated in many enzymes, including aldehyde dehydrogenases. Here we show that the uncharacterized protein BetB (SA2613) from Staphylococcus aureus is a highly specific betaine aldehyde dehydrogenase, which exhibits substrate inhibition at concentrations of betaine aldehyde as low as 0.15 mM. In contrast, the aldehyde dehydrogenase YdcW from Escherichia coli, which is also active against betaine aldehyde, shows no inhibition by this substrate. Using the crystal structures of BetB and YdcW, we performed a structure-based mutational analysis of BetB and introduced the YdcW residues into the BetB active site. From a total of 32 mutations, those in five residues located in the substrate binding pocket (Val288, Ser290, His448, Tyr450, and Trp456) greatly reduced the substrate inhibition of BetB, whereas the double mutant protein H448F/Y450L demonstrated a complete loss of substrate inhibition. Substrate inhibition was also reduced by mutations of the semiconserved Gly234 (to Ser, Thr, or Ala) located in the BetB NAD(+) binding site, suggesting some cooperativity between the cofactor and substrate binding sites. Substrate docking analysis of the BetB and YdcW active sites revealed that the wild-type BetB can bind betaine aldehyde in both productive and nonproductive conformations, whereas only the productive binding mode can be modeled in the active sites of YdcW and the BetB mutant proteins with reduced substrate inhibition. Thus, our results suggest that the molecular mechanism of substrate inhibition of BetB is associated with the nonproductive binding of betaine aldehyde. Structure-based mutational studies of substrate inhibition of betaine aldehyde dehydrogenase BetB from Staphylococcus aureus.,Chen C, Joo JC, Brown G, Stolnikova E, Halavaty AS, Savchenko A, Anderson WF, Yakunin AF Appl Environ Microbiol. 2014 Jul;80(13):3992-4002. doi: 10.1128/AEM.00215-14., Epub 2014 Apr 18. PMID:24747910 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldehyde dehydrogenase 3D structures

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