2J6L

Structure of aminoadipate-semialdehyde dehydrogenase

Summary for 2J6L

• Entry DOI: 10.2210/pdb2j6l/pdb
• Descriptor: ALDEHYDE DEHYDROGENASE FAMILY 7 MEMBER A1, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, BROMIDE ION, ... (5 entities in total)
• Functional Keywords: aldehyde dehydrogenase, nad, reductase, oxidoreductase, lysine catabolism
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Mitochondrion . Isoform 2: Cytoplasm, cytosol: P49419
• Total number of polymer chains: 8
• Total formula weight: 440062.82

Authors

Bunkoczi, G.,Guo, K.,Debreczeni, J.E.,Smee, C.,Arrowsmith, C.,Edwards, A.,Sundstrom, M.,Weigelt, J.,von Delft, F.,Oppermann, U. (deposition date: 2006-09-29, release date: 2006-10-12, Last modification date: 2023-12-13)

Primary citation

Brocker, C.,Lassen, N.,Estey, T.,Pappa, A.,Cantore, M.,Orlova, V.V.,Chavakis, T.,Kavanagh, K.L.,Oppermann, U.,Vasiliou, V.
Aldehyde Dehydrogenase 7A1 (Aldh7A1) is a Novel Enzyme Involved in Cellular Defense Against Hyperosmotic Stress.
J.Biol.Chem., 285:18452-, 2010

PubMed Abstract: Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. Human ALDH7A1 expression in Chinese hamster ovary cells attenuated osmotic stress-induced apoptosis caused by increased extracellular concentrations of sucrose or sodium chloride. Purified recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates, including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde. The crystal structure for ALDH7A1 supports the enzyme's substrate specificities. Tissue distribution studies in mice showed the highest expression of ALDH7A1 protein in liver, kidney, and brain, followed by pancreas and testes. ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria, making it unique among the aldehyde dehydrogenase enzymes. Analysis of human and mouse cDNA sequences revealed mitochondrial and cytosolic transcripts that are differentially expressed in a tissue-specific manner in mice. In conclusion, ALDH7A1 is a novel aldehyde dehydrogenase expressed in multiple subcellular compartments that protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes.

PubMed: 20207735
DOI: 10.1074/JBC.M109.077925

Experimental method

X-RAY DIFFRACTION (1.3 Å)