title: Structural basis for cofactor and substrate selection by cyanobacterium succinic semialdehyde dehydrogenase.
abstract: Aldehyde dehydrogenase (ALDH) catalyzes the oxidation of aldehydes to carboxylic acids. Cyanobacterium Synechococcus contains one ALDH enzyme (Sp2771), together with a novel 2-oxoglutarate decarboxylase, to complete a non-canonical tricarboxylic acid cycle. However, the molecular mechanisms for substrate selection and cofactor preference by Sp2771 are largely unknown. Here, we report crystal structures of wild type Sp2771, Sp2771 S419A mutant and ternary structure of Sp2771 C262A mutant in complex with NADP(+) and SSA, as well as binary structure of Gluconobacter oxydans aldehyde dehydrogenase (Gox0499) in complex with PEG. Structural comparison of Sp2771 with Gox0499, coupled with mutational analysis, demonstrates that Ser157 residue in Sp2771 and corresponding Pro159 residue in Gox0499 play critical structural roles in determining NADP(+) and NAD(+) preference for Sp2771 and Gox0499, respectively, whereas size and distribution of hydrophobic residues along the substrate binding funnel determine substrate selection. Hence, our work has provided insightful structural information into cofactor and substrate selection by ALDH.
authors.affiliation: Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Zuanning
authors.initials: Z
authors.lastname: Yuan
authors.forename: Bo
authors.initials: B
authors.lastname: Yin
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Wei
authors.forename: Yu-ren Adam
authors.initials: YR
authors.lastname: Yuan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D002952:Citric Acid Cycle; D003067:Coenzymes / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D000458:Cyanobacteria / Q000201:enzymology*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013379:Substrate Specificity; D050644:Succinate-Semialdehyde Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D003067:Coenzymes; D050644:Succinate-Semialdehyde Dehydrogenase