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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1o04

E.C. namealdehyde dehydrogenase (NAD+)
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 1.2.1.3
CSA Homologues of 1o04There are 26 Homologs
CSA Entries With UniProtID P05091
CSA Entries With EC Number 1.2.1.3
PDBe Entry 1o04
PDBSum Entry 1o04
MACiE Entry 1o04

Literature Report

IntroductionAldehyde dehydrogenase(ALDH) catalyses the oxidation of toxic aldehydes to their corresponding acids, using NAD. The human mitochondrial form of ALDH is called class 2 ALDH.
MechansimThe catalysis follows a sequential mechanism in which NAD+ binds prior to aldehyde. The aldehyde then undergoes nucleophilic attack by Cys302, forming a covalent intermediate. Next, the carbonyl hydride is transferred to the A-side of the nicotinamide ring. In the rate-limiting step, Glu268 activates a water molecule for nucleophilic attack at the acyl-sulphur bond, releasing the acid product prior to NADH dissociation. Lys192 and Glu399 stabilise the transition state during the hydride transfer.
Reaction

Catalytic Sites for 1o04

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysA192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluA268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluA399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerB302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysB192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluB268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluB399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerC302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysC192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluC268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluC399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerD302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysD192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluD268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluD399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerE302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysE192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluE268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluE399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerF302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysF192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluF268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluF399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Annotated By Reference To The Literature - Site 7 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerG302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysG192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluG268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluG399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Annotated By Reference To The Literature - Site 8 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerH302319macie:sideChainIt acts as a nucleophile to attack the aldehyde to form a covalent enzyme-substrate intermediate.
LysH192209macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.
GluH268285macie:sideChainIt acts as a base to deprotonate a water molecule for nucleophilic attack at the acyl-sulphur bond.
GluH399416macie:sideChainIt stabilises the transition state during hydride transfer from the enzyme-substrate intermediate to NAD+.

Literature References

Notes:
Farr├ęs J
Investigation of the active site cysteine residue of rat liver mitochondrial aldehyde dehydrogenase by site-directed mutagenesis.
Biochemistry 1995 34 2592-2598
PubMed: 7873540
Wang X
Involvement of glutamate 268 in the active site of human liver mitochondrial (class 2) aldehyde dehydrogenase as probed by site-directed mutagenesis.
Biochemistry 1995 34 237-243
PubMed: 7819202
Ni L
Involvement of glutamate 399 and lysine 192 in the mechanism of human liver mitochondrial aldehyde dehydrogenase.
J Biol Chem 1997 272 18823-18826
PubMed: 9228057
Sheikh S
The potential roles of the conserved amino acids in human liver mitochondrial aldehyde dehydrogenase.
J Biol Chem 1997 272 18817-18822
PubMed: 9228056
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