2uuv
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Ether phospholipids are essential constituents of eukaryotic cell | + | 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== | ==About this Structure== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:50:26 2008'' |
Revision as of 16:50, 21 February 2008
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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 and 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
Page seeded by OCA on Thu Feb 21 18:50:26 2008
Categories: Alkylglycerone-phosphate synthase | Dictyostelium discoideum | Single protein | Aliverti, A. | Carpanelli, E. | Coda, A. | Mattevi, A. | Mattiroli, F. | Pandini, V. | Razeto, A. | FAD | PL3 | Biosynthesis of phospholipids | Fad | Flavin | Flavoprotein | Lipid synthesis | Peroxisomal disorder | Peroxisome | Plasmalogens | Rhizomelic chondrodysplasia punctata | Transferase
