spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1s9c

E.C. name
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 1.1.1
CSA Homologues of 1s9cThere are 17 Homologs
CSA Entries With UniProtID P51659
CSA Entries With EC Number 1.1.1
PDBe Entry 1s9c
PDBSum Entry 1s9c
MACiE Entry 1s9c

Literature Report

IntroductionHuman 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 hydratase function reversibly catalyses the addition of water to the beta-carbon of trans-2-enoyl-CoAs with (R) specificity (the opposite to MFE-1).
Mechansim The water residue is activated as a nucleophile by the side chains of Asp 193 and His 198 (both are deprotonated, and coordinate the protons on water, with the carbonyl of Ile 213 reducing the pKa of His 198). A lone pair on water attacks C3 of the enoyl substrate (the electrophilic alkene). The reaction is proposed to have a concerted transition state, where the water proton coordinated to His 813 is delivered to C2 of the substrate, and the bond between that proton and the oxygen of water begins to break. The partial negative charge on the thioester oxygen in the transition state is stabilised by the backbone amide of Gly 216.
Thus, the overall reaction adds hydroxide from water to the C3 carbon of the substrate, and the proton from the same water molecule to the C2 carbon.
Reaction

Catalytic Sites for 1s9c

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyA216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspA193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisA198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleA213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyB216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspB193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisB198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleB213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyC216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspC193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisC198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleC213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyD216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspD193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisD198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleD213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyE216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspE193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisE198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleE213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyF216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspF193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisF198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleF213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 7 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyG216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspG193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisG198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleG213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 8 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyH216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspH193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisH198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleH213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 9 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyI216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspI193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisI198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleI213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 10 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyJ216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspJ193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisJ198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleJ213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 11 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyK216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspK193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisK198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleK213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Annotated By Reference To The Literature - Site 12 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyL216533macie:mainChainAmideThe main chain amide group of Gly 216 hydrogen bonds to the carbonyl group of the substrate and stabilises the build up of negative charge in the transition state.
AspL193510macie:sideChainAsp 193 coordinates and activates a water molecule using its side chain.
HisL198515macie:sideChainHis 198 is deprotonated and coordinates the water molecule via the proton, activating water as a nucleophile. This proton is delivered to the substrate.
IleL213530macie:mainChainCarbonylThe main chain carbonyl group of Ile 213 hydrogen bonds to His 198, thus lowering the pKa of His 198.

Literature References

Notes:The residue numbering in this CSA entry reflects the PDB residue numbering - i.e. for just the hydratase unit of MFE-2. The numbering of residues in the literature reflects the numbering in the three-unit MFE-2, which is: Asp 510, His 515, Ile 530, Gly 533.
Koski KM
Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal multifunctional enzyme type 2.
J Mol Biol 2005 345 1157-1169
PubMed: 15644212
Qin YM
Human peroxisomal multifunctional enzyme type 2. Site-directed mutagenesis studies show the importance of two protic residues for 2-enoyl-CoA hydratase 2 activity.
J Biol Chem 2000 275 4965-4972
PubMed: 10671535
Koski MK
A two-domain structure of one subunit explains unique features of eukaryotic hydratase 2.
J Biol Chem 2004 279 24666-24672
PubMed: 15051722
spacer
spacer