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Catalytic Site Atlas

CSA LITERATURE entry for 1mka

E.C. name3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz)
CSA Homologues of 1mkaThere are 25 Homologs
CSA Entries With UniProtID P0A6Q3
CSA Entries With EC Number
PDBe Entry 1mka
PDBSum Entry 1mka
MACiE Entry M0010

Literature Report

IntroductionIn Escherichia coli, the enzyme beta-hydroxydecanoyl thiol ester dehydrase is responsible for the key step, where an unsaturated intermediate in the biosynthetic pathway of saturated fatty acids is intercepted and shunted into the pathway leading to unsaturated products. Dehydrase catalyses two reactions on fatty acid thiol esters of acyl carrier protein (ACP): the dehydration of (R)-3-hydroxydecanoyl-ACP to (E)-2-decenoyl-ACP, a reaction that also occurs in the elongation of saturated fatty acids; and the isomerization of (E)-2-decenoyl-ACP to (Z)-3-decenoyl-ACP. (E)-2-decenoyl-ACP can be reduced to decanoyl-ACP, which is elongated to the usual saturated fatty acids; in contrast, the cis (Z) double bond of (Z)-3-decenoyl-ACP is retained through the further cycles of fatty-acid elongation. The isomerisation catalysed by dehydrase is an allylic rearrangement, which is a relatively simple, single-substrate reaction. Both the dehydration and isomerization reactions seem to occur in the same active site.
3-hydroxydecanoyl-[acyl-carrier protein] dehydratase (dehydrase) is required for the biosynthesis of unsaturated fatty acids, by shunting a 10-carbon intermediate from the saturated fatty acid pathway into the unsaturated fatty acid pathway.
Dehydratase catalyses dehydration and isomerisation reactions by a mechanism that does not involve metals or other cofactors, unlike the majority of the enzymes that catalyse similar reactions. The catalytic site is isolated from solution and is predominantly hydrophobic apart from histidine (A HIS 70) and aspartic acid (B ASP 84), which together are proposed to catalyse the reactions. The reactions take place in a bifunctional active site.
MechansimThe dehydration reaction proceeds as follows: His70 deprotonates the substrate, initiating double bond rearrangement and the formation of an oxyanion. The oxyanion collapses, initiating double bond rearrangement and the elimination of water with concomitant deprotonation of Asp84B.
Peptide dipoles from GLY 79 and CYS 80 at the N terminus of the central alpha helix (alpha 3) may provide stabilisation to the presumed enol/enolate intermediate and to the leaving hydroxyl group.
HIS 70 in the free enzyme donates a proton in a hydrogen bond, to the backbone carbonyl of VAL 76. This is consistent with the catalytic role for histidine, because this results in a basic lone pair of electrons. The hydrogen bond also positions the imidazole ring rather precisely. Thus we infer that HIS 70 is in the correct tautomeric state and optimal orientation for catalysis in the free enzyme.

Catalytic Sites for 1mka

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA7071macie:sideChainActs as a a base to deprotonate the fatty acid to initiate double bond rearrangement.
AspA8485macie:sideChainActs as a general acid to protonate the leaving hydroxyl group to form water.
ValA7677macie:mainChainCarbonylForms a hydrogen bond to His70 to ensure correct tautomeric state and orientation.
GlyA7980macie:mainChainAmideStabilises negative charge build up, by hydrogen bonding to form an oxyanion hole.
CysA8081macie:mainChainAmideStabilises negative charge build up, by hydrogen bonding to form an oxyanion hole.

Literature References

Leesong M
Structure of a dehydratase-isomerase from the bacterial pathway for biosynthesis of unsaturated fatty acids: two catalytic activities in one active site.
Structure 1996 4 253-264
PubMed: 8805534