The crucial step in ether phospholipid biosynthesis: structural basis of a noncanonical reaction associated with a peroxisomal disorder
Articolo
Data di Pubblicazione:
2007
Citazione:
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. - In: STRUCTURE. - ISSN 0969-2126. - 15:6(2007 Jun 13), pp. 683-692.
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
alkyl-dihydroxyacetonephosphate synthese; Guinea-pig liver; alkyldihydroxyacetone-P synthase; ehrlich ascites tumor; nucleotide-sequence; lipid biosynthesis; acyldhydroxyacetone phosphate; macromolecular structures; bond formation; mechanism
Elenco autori:
A. Razeto, F. Mattiroli, E. Carpanelli, A. Aliverti, V. Pandini, A. Coda, A. Mattevi
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