1o04 | pdb_00001o04

Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+

spinqualitylabelsall models 1o04, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1o04 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, GAI, MG, NA, NAD Related: 1cw3, 1ag8, 1a4z, 1nzw, 1nzx, 1nzz, 1o00, 1o01, 1o02, 1o05 Gene: ALDH2 OR ALDM (HUMAN) Activity: Aldehyde dehydrogenase (NAD(+)), with EC number 1.2.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Crystal structures of many enzymes in the aldehyde dehydrogenase superfamily determined in the presence of bound NAD(P)(+) have exhibited conformational flexibility for the nicotinamide half of the cofactor. This has been hypothesized to be important in catalysis because one conformation would block the second half of the reaction, but no firm evidence has been put forth which shows whether the oxidized and reduced cofactors preferentially occupy the two observed conformations. We present here two structures of the wild type and two structures of a Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase in binary complexes with NAD(+) and NADH. These structures, including the Cys302Ser mutant in complex with NAD(+) at 1.4 A resolution and the wild-type enzyme in complex with NADH at 1.9 A resolution, provide strong evidence that bound NAD(+) prefers an extended conformation ideal for hydride transfer and bound NADH prefers a contracted conformation ideal for acyl-enzyme hydrolysis. Unique interactions between the cofactor and the Rossmann fold make isomerization possible while allowing the remainder of the active site complex to remain intact. In addition, these structures clarify the role of magnesium in activating the human class 2 enzyme. Our data suggest that the presence of magnesium may lead to selection of particular conformations and speed isomerization of the reduced cofactor following hydride transfer. Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase.,Perez-Miller SJ, Hurley TD Biochemistry. 2003 Jun 17;42(23):7100-9. PMID:12795606 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldehyde dehydrogenase 3D structures

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