PDBsum entry 2uuv

Transferase

PDB id: 2uuv

Contents

Protein chains

523 a.a. *

491 a.a. *

Ligands

FAD ×4

PL3 ×3

Waters ×1134

* Residue conservation analysis

PDB id:

2uuv

Name:

Transferase

Title:

Alkyldihydroxyacetonephosphate synthase in p1

Structure:

Alkyldihydroxyacetonephosphate synthase. Chain: a, b, c, d. Fragment: residues 9-587. Synonym: alkyl-dhap synthase, alkylglycerone-phosphate synthase. Engineered: yes

Source:

Dictyostelium discoideum. Slime mold. Organism_taxid: 44689. Strain: kassx-3. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plys. Other_details: academia DNA sequencing center in collaboration with dictyostelium cdna project

Resolution:

1.99Å R-factor: 0.228 R-free: 0.264

Authors:

A.Razeto,F.Mattiroli,E.Carpanelli,A.Aliverti,V.Pandini,A.Coda, A.Mattevi

Key ref:

A.Razeto et al. (2007). The crucial step in ether phospholipid biosynthesis: structural basis of a noncanonical reaction associated with a peroxisomal disorder. Structure, 15, 683-692. PubMed id: 17562315 DOI: 10.1016/j.str.2007.04.009

Date:

07-Mar-07 Release date: 26-Jun-07

Protein chains

O96759  (ADAS_DICDI) -  Alkyldihydroxyacetonephosphate synthase from Dictyostelium discoideum

Seq: 611 a.a.

Struc: 523 a.a.

Protein chain

O96759  (ADAS_DICDI) -  Alkyldihydroxyacetonephosphate synthase from Dictyostelium discoideum

Seq: 611 a.a.

Struc: 491 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.2.5.1.26 - alkylglycerone-phosphate synthase.
• Reaction: a long chain fatty alcohol + a 1-acylglycerone 3-phosphate = a 1-O- alkylglycerone 3-phosphate + a long-chain fatty acid + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.str.2007.04.009

Structure 15:683-692 (2007)

PubMed id: 17562315

The crucial step in ether phospholipid biosynthesis: structural basis of a noncanonical reaction associated with a peroxisomal disorder.

A.Razeto, F.Mattiroli, E.Carpanelli, A.Aliverti, V.Pandini, A.Coda, A.Mattevi.

ABSTRACT

Ether phospholipids are essential constituents of eukaryotic cell membranes. Rhizomelic chondrodysplasia punctata type 3 is a severe peroxisomal disorder caused by inborn deficiency of alkyldihydroxyacetonephosphate synthase (ADPS). The enzyme carries out the most characteristic step in ether phospholipid biosynthesis: formation of the ether bond. The crystal structure of ADPS from Dictyostelium discoideum shows a fatty-alcohol molecule bound in a narrow hydrophobic tunnel, specific for aliphatic chains of 16 carbons. Access to the tunnel is controlled by a flexible loop and a gating helix at the protein-membrane interface. Structural and mutagenesis investigations identify a cluster of hydrophilic catalytic residues, including an essential tyrosine, possibly involved in substrate proton abstraction, and the arginine that is mutated in ADPS-deficient patients. We propose that ether bond formation might be orchestrated through a covalent imine intermediate with the flavin, accounting for the noncanonical employment of a flavin cofactor in a nonredox reaction.

Selected figure(s)

Figure 5.
Figure 5. Electrostatic Potentials of the ADPS Dimer Surface
Red, blue, and white show potentials at −8, +8, and 0 k[B]T e^−1, respectively. The basic amino acids forming the membrane-binding region are labeled.

Figure 7.
Figure 7. Structural Framework for ADPS Catalysis
(A) A structural framework for the reaction cycle of ADPS. Step 1, ADPS binds the acyl-DHAP substrate; the HHH loop becomes ordered and the gating helix closes the tunnel. Step 2, the fatty-acid product (R[1]COOH) is generated and released, whereas the DHAP moiety remains trapped in the active site. Step 3, the fatty alcohol (R[2]OH) binds in the tunnel. Step 4, the alkyl-DHAP product is formed and released.
(B) Working hypothesis for the reaction mechanism of ADPS.

The above figures are reprinted by permission from Cell Press: Structure (2007, 15, 683-692) copyright 2007.

Figures were selected by an automated process.