2uuv: Difference between revisions

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==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.

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==

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[[Category: transferase]]

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 34: / Line 34: @@
 [[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:47:11 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:50:26 2008''