2uuv

From Proteopedia

Revision as of 18:06, 18 December 2007

ALKYLDIHYDROXYACETONEPHOSPHATE SYNTHASE IN P1

Overview

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.

About this Structure

2UUV is a Single protein structure of sequence from Dictyostelium discoideum with FAD and PL3 as ligands. Active as Alkylglycerone-phosphate synthase, with EC number 2.5.1.26 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The crucial step in ether phospholipid biosynthesis: structural basis of a noncanonical reaction associated with a peroxisomal disorder., Razeto A, Mattiroli F, Carpanelli E, Aliverti A, Pandini V, Coda A, Mattevi A, Structure. 2007 Jun;15(6):683-92. PMID:17562315

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