PDBsum entry 1cw3

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
(+ 2 more) 494 a.a. *
NAD ×8
_MN ×8
_MG ×8
Waters ×1087
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Human mitochondrial aldehyde dehydrogenase complexed with NAD+ and mn2+
Structure: Mitochondrial aldehyde dehydrogenase. Chain: a, b, c, d, e, f, g, h. Fragment: complete mature sequence (does not include mitochondrial leader sequence). Synonym: aldhi, aldh-e2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Octamer (from PQS)
2.58Å     R-factor:   0.175     R-free:   0.242
Authors: L.Ni,J.Zhou,T.D.Hurley,H.Weiner
Key ref: L.Ni et al. (1999). Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms. Protein Sci, 8, 2784-2790. PubMed id: 10631996 DOI: 10.1110/ps.8.12.2784
25-Aug-99     Release date:   31-Aug-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P05091  (ALDH2_HUMAN) -  Aldehyde dehydrogenase, mitochondrial
517 a.a.
494 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Aldehyde dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An aldehyde + NAD+ + H2O = a carboxylate + NADH
Bound ligand (Het Group name = NAD)
corresponds exactly
+ H(2)O
= carboxylate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular vesicular exosome   3 terms 
  Biological process     metabolic process   10 terms 
  Biochemical function     electron carrier activity     5 terms  


DOI no: 10.1110/ps.8.12.2784 Protein Sci 8:2784-2790 (1999)
PubMed id: 10631996  
Human liver mitochondrial aldehyde dehydrogenase: three-dimensional structure and the restoration of solubility and activity of chimeric forms.
L.Ni, J.Zhou, T.D.Hurley, H.Weiner.
Human liver cytosolic and mitochondrial isozymes of aldehyde dehydrogenase share 70% sequence identity. However, the first 21 residues are not conserved between the human isozymes (15% identity). The three-dimensional structures of the beef mitochondrial and sheep cytosolic forms have virtually identical three-dimensional structures. Here, we solved the structure of the human mitochondrial enzyme and found it to be identical to the beef enzyme. The first 21 residues are found on the surface of the enzyme and make no contact with other subunits in the tetramer. A pair of chimeric enzymes between the human isozymes was made. Each chimera had the first 21 residues from one isozyme and the remaining 479 from the other. When the first 21 residues were from the mitochondrial isozyme, an enzyme with cytosolic-like properties was produced. The other was expressed but was insoluble. It was possible to restore solubility and activity to the chimera that had the first 21 cytosolic residues fused to the mitochondrial ones by making point mutations to residues at the N-terminal end. When residue 19 was changed from tyrosine to a cysteine, the residue found in the mitochondrial form, an active enzyme could be made though the Km for NAD+ was 35 times higher than the native mitochondrial isozyme and the specific activity was reduced by 75%. This residue interacts with residue 203, a nonconserved, nonactive site residue. A mutation of residue 18, which also interacts with 203, restored solubility, but not activity. Mutation to residue 15, which interacts with 104, also restored solubility but not activity. It appears that to have a soluble or active enzyme a favorable interaction must occur between a residue in a surface loop and a residue elsewhere in the molecule even though neither make contact with the active site region of the enzyme.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20062057 S.Perez-Miller, H.Younus, R.Vanam, C.H.Chen, D.Mochly-Rosen, and T.D.Hurley (2010).
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.
  Nat Struct Mol Biol, 17, 159-164.
PDB codes: 3inj 3inl
19911309 C.Y.Kim, C.Webster, J.K.Roberts, J.H.Moon, E.Z.Alipio Lyon, H.Kim, M.Yu, L.W.Hung, and T.C.Terwilliger (2009).
Analysis of nucleoside-binding proteins by ligand-specific elution from dye resin: application to Mycobacterium tuberculosis aldehyde dehydrogenases.
  J Struct Funct Genomics, 10, 291-301.  
19292760 M.C.Long, D.A.Nagegowda, Y.Kaminaga, K.K.Ho, C.M.Kish, J.Schnepp, D.Sherman, H.Weiner, D.Rhodes, and N.Dudareva (2009).
Involvement of snapdragon benzaldehyde dehydrogenase in benzoic acid biosynthesis.
  Plant J, 59, 256-265.  
17173928 L.Di Costanzo, G.A.Gomez, and D.W.Christianson (2007).
Crystal structure of lactaldehyde dehydrogenase from Escherichia coli and inferences regarding substrate and cofactor specificity.
  J Mol Biol, 366, 481-493.
PDB codes: 2hg2 2ilu 2imp
15983043 H.N.Larson, H.Weiner, and T.D.Hurley (2005).
Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase "Asian" variant.
  J Biol Chem, 280, 30550-30556.
PDB code: 1zum
15659684 K.K.Ho, and H.Weiner (2005).
Isolation and characterization of an aldehyde dehydrogenase encoded by the aldB gene of Escherichia coli.
  J Bacteriol, 187, 1067-1073.  
15689506 S.Idicula-Thomas, and P.V.Balaji (2005).
Understanding the relationship between the primary structure of proteins and its propensity to be soluble on overexpression in Escherichia coli.
  Protein Sci, 14, 582-592.  
12081471 J.S.Rodriguez-Zavala, and H.Weiner (2002).
Structural aspects of aldehyde dehydrogenase that influence dimer-tetramer formation.
  Biochemistry, 41, 8229-8237.  
11468345 J.Zhou, and H.Weiner (2001).
The N-terminal portion of mature aldehyde dehydrogenase affects protein folding and assembly.
  Protein Sci, 10, 1490-1497.  
10819999 B.Wei, L.Ni, T.D.Hurley, and H.Weiner (2000).
Cooperativity in nicotinamide adenine dinucleotide binding induced by mutations of arginine 475 located at the subunit interface in the human liver mitochondrial class 2 aldehyde dehydrogenase.
  Biochemistry, 39, 5295-5302.  
11009616 J.Zhou, and H.Weiner (2000).
Basis for half-of-the-site reactivity and the dominance of the K487 oriental subunit over the E487 subunit in heterotetrameric human liver mitochondrial aldehyde dehydrogenase.
  Biochemistry, 39, 12019-12024.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.