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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1gz6

E.C. name
SpeciesRattus norvegicus (Rat)
E.C. Number (IntEnz) 1.1.1
CSA Homologues of 1gz6There are 469 Homologs
CSA Entries With UniProtID P97852
CSA Entries With EC Number 1.1.1
PDBe Entry 1gz6
PDBSum Entry 1gz6
MACiE Entry 1gz6

Literature Report

IntroductionMammalian peroxisomal multifunctional enzyme type 2 (MFE-2) is important in the beta-oxidation of very-long-chain and alpha-methyl-branched fatty acids as well as the synthesis of bile acids. It has three units: a dehydrogenase unit, an sterol carrier protein (SCP) -like unit and a central hydratase unit.
The dehydrogenase unit oxidises the C3 hydroxyl group of (3R)-hydroxyacyl-CoA molecules to obtain the corresponding (3R)-ketoacyl-CoA. It belongs to the short chain alcohol dehydrogenase/reductase (SDR) superfamily.
Mechansim Lys 168 is protonated and decreases the pKa of Tyr 164 so that Tyr is deprotonated. Tyr 164 can then deprotonate the hydroxy group of 3-hydroxyacyl-CoA. The reaction is concerted (E1-like elimination of H2) so that the deprotonation occurs at the same time as the C3 hydride is delivered to NAD+. Ser 151 may stabilise the transition state (it hydrogen bonds to the substrate hydroxyl group) but its role is thought to be mainly to ensure correct orientation of the substrate. The oxidised product is 3-ketoacyl CoA.
Reaction

Catalytic Sites for 1gz6

Annotated By Reference To The Literature - Site 9 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA164164macie:sideChainTyr 164 exists in the deprotonated form. It acts as a general base to deprotonate the hydroxy group of the substrate.
LysA168168macie:sideChainLys 168 lowers the pKa of Tyr 164 so that Tyr can exist in its deprotonated form.

Annotated By Reference To The Literature - Site 10 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrB164164macie:sideChainTyr 164 exists in the deprotonated form. It acts as a general base to deprotonate the hydroxy group of the substrate.
LysB168168macie:sideChainLys 168 lowers the pKa of Tyr 164 so that Tyr can exist in its deprotonated form.

Annotated By Reference To The Literature - Site 11 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrC164164macie:sideChainTyr 164 exists in the deprotonated form. It acts as a general base to deprotonate the hydroxy group of the substrate.
LysC168168macie:sideChainLys 168 lowers the pKa of Tyr 164 so that Tyr can exist in its deprotonated form.

Annotated By Reference To The Literature - Site 12 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrD164164macie:sideChainTyr 164 exists in the deprotonated form. It acts as a general base to deprotonate the hydroxy group of the substrate.
LysD168168macie:sideChainLys 168 lowers the pKa of Tyr 164 so that Tyr can exist in its deprotonated form.

Literature References

Notes:
Haapalainen AM
Binary structure of the two-domain (3R)-hydroxyacyl-CoA dehydrogenase from rat peroxisomal multifunctional enzyme type 2 at 2.38 A resolution.
Structure 2003 11 87-97
PubMed: 12517343
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