3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ
FabZ is the primary dehydratase involved in fatty-acid elongation in type II fatty acid biosynthesis (FAS). Involved in unsaturated fatty acids biosynthesis. Catalyses the dehydration of short chain beta-hydroxyacyl-ACPs and long chain saturated and unsaturated beta-hydroxyacyl-ACPs.
Reference Protein and Structure
- Sequence
-
Q9HXY7
(4.2.1.59)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Pseudomonas aeruginosa PAO1 (Bacteria)
- PDB
-
1u1z
- The Structure of (3R)-hydroxyacyl-ACP dehydratase (FabZ)
(2.5 Å)
- Catalytic CATH Domains
-
3.10.129.10
(see all for 1u1z)
Enzyme Reaction (EC:4.2.1.59)
→
+
Alternative enzyme names: FabZ (gene name), FabA (gene name), D-3-hydroxyoctanoyl-[acyl carrier protein] dehydratase, Beta-hydroxyoctanoyl-acyl carrier protein dehydrase, Beta-hydroxyoctanoyl thioester dehydratase, Beta-hydroxyoctanoyl-ACP-dehydrase, (3R)-3-hydroxyoctanoyl-[acyl-carrier-protein] hydro-lyase, (3R)-3-hydroxyoctanoyl-[acyl-carrier-protein] hydro-lyase (oct-2-enoyl-[acyl-carrier protein]-forming), 3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase,
Enzyme Mechanism
Introduction
The two base hypothesis for the dehydration reaction proceeds as follows: His49 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 Glu63B.
Catalytic Residues Roles
| UniProt | PDB* (1u1z) | ||
| Glu63 | Glu63(83)B | Acts as a general acid/base. Donates a proton to the leaving water molecule. | proton acceptor, proton donor |
| His49 | His49(69)A | Acts as a general acid/base. It performs the initial proton abstraction from the substrate. | proton acceptor, proton donor |
| Ile55 (main-C) | Ile55(75)A (main-C) | His49 in the free enzyme donates a proton in a hydrogen bond, to the backbone carbonyl of Ile55. 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. | electrostatic stabiliser |
| Gly58 (main-N), Val59 (main-N) | Gly58(78)A (main-N), Val59(79)A (main-N) | Peptide dipoles from Gly58 and Val59 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. | electrostatic stabiliser |
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file;
y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain;
C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.
Chemical Components
proton transfer, intermediate formation, unimolecular elimination by the conjugate base, dehydration, native state of enzyme regenerated, inferred reaction stepReferences
- Moynié L et al. (2013), J Mol Biol, 425, 365-377. Structural Insights into the Mechanism and Inhibition of the β-Hydroxydecanoyl-Acyl Carrier Protein Dehydratase from Pseudomonas aeruginosa. DOI:10.1016/j.jmb.2012.11.017. PMID:23174186.
- Zhang L et al. (2008), J Biol Chem, 283, 5370-5379. Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ). DOI:10.1074/jbc.M705566200. PMID:18093984.
- Kimber MS et al. (2004), J Biol Chem, 279, 52593-52602. The Structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) fromPseudomonas aeruginosa. DOI:10.1074/jbc.m408105200. PMID:15371447.
- Heath RJ et al. (1996), J Biol Chem, 271, 27795-27801. Roles of the FabA and FabZ -Hydroxyacyl-Acyl Carrier Protein Dehydratases in Escherichia coli Fatty Acid Biosynthesis. DOI:10.1074/jbc.271.44.27795.
Step 1. His49 abstracts a proton from the ACP substrate forming an oxyanion intermediate.
Download: Image, Marvin FileCatalytic Residues Roles
| Residue | Roles |
|---|---|
| Ile55(75)A (main-C) | electrostatic stabiliser |
| Gly58(78)A (main-N) | electrostatic stabiliser |
| Val59(79)A (main-N) | electrostatic stabiliser |
| Val59(79)A (main-N) | ground state destabiliser |
| His49(69)A | proton acceptor |
Chemical Components
proton transfer, intermediate formation
Step 2. The oxyanion intermediate collapses, deprotonating Glu63 to form the trans-product.
Download: Image, Marvin FileCatalytic Residues Roles
| Residue | Roles |
|---|---|
| Ile55(75)A (main-C) | electrostatic stabiliser |
| Gly58(78)A (main-N) | electrostatic stabiliser |
| Val59(79)A (main-N) | electrostatic stabiliser |
| Glu63(83)B | proton donor |
Chemical Components
ingold: unimolecular elimination by the conjugate base, dehydration, proton transfer
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| His49(69)A | proton donor |
| Glu63(83)B | proton acceptor |
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