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PDBsum entry 2j6l

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
2j6l
Jmol PyMol
Contents
Protein chain
(+ 2 more) 497 a.a. *
Ligands
NAI ×8
Metals
_NA ×8
_BR ×15
Waters ×5031
* Residue conservation analysis
PDB id:
2j6l
Name: Oxidoreductase
Title: Structure of aminoadipate-semialdehyde dehydrogenase
Structure: Aldehyde dehydrogenase family 7 member a1. Chain: a, b, c, d, e, f, g, h. Synonym: antiquitin-1, aminoadipate-semialdehyde dehydrogen engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: r3.
Biol. unit: Tetramer (from PDB file)
Resolution:
1.30Å     R-factor:   0.140     R-free:   0.189
Authors: G.Bunkoczi,K.Guo,J.E.Debreczeni,C.Smee,C.Arrowsmith,A.Edward M.Sundstrom,J.Weigelt,F.Von Delft,U.Oppermann
Key ref: C.Brocker et al. (2010). Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. J Biol Chem, 285, 18452-18463. PubMed id: 20207735
Date:
29-Sep-06     Release date:   12-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P49419  (AL7A1_HUMAN) -  Alpha-aminoadipic semialdehyde dehydrogenase
Seq:
Struc:
 
Seq:
Struc:
539 a.a.
497 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 2: E.C.1.2.1.3  - Aldehyde dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An aldehyde + NAD+ + H2O = a carboxylate + NADH
aldehyde
+
NAD(+)
Bound ligand (Het Group name = NAI)
corresponds exactly
+ H(2)O
= carboxylate
+ NADH
   Enzyme class 3: E.C.1.2.1.31  - L-aminoadipate-semialdehyde dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: (S)-2-amino-6-oxohexanoate + NAD(P)(+) + H2O = L-2-aminoadipate + NAD(P)H
(S)-2-amino-6-oxohexanoate
+
NAD(P)(+)
Bound ligand (Het Group name = NAI)
matches with 91.67% similarity
+ H(2)O
= L-2-aminoadipate
+ NAD(P)H
   Enzyme class 4: E.C.1.2.1.8  - Betaine-aldehyde dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Betaine aldehyde + NAD+ + H2O = betaine + NADH
Betaine aldehyde
+
NAD(+)
Bound ligand (Het Group name = NAI)
corresponds exactly
+ H(2)O
= betaine
+ NADH
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   6 terms 
  Biological process     metabolic process   7 terms 
  Biochemical function     protein binding     5 terms  

 

 
    reference    
 
 
J Biol Chem 285:18452-18463 (2010)
PubMed id: 20207735  
 
 
Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress.
C.Brocker, N.Lassen, T.Estey, A.Pappa, M.Cantore, V.V.Orlova, T.Chavakis, K.L.Kavanagh, U.Oppermann, V.Vasiliou.
 
  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.
 

 

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