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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2007-6-12
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0969-2126
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
683-92
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pubmed:meshHeading |
pubmed-meshheading:17562315-Alkyl and Aryl Transferases,
pubmed-meshheading:17562315-Amino Acid Sequence,
pubmed-meshheading:17562315-Amino Acid Substitution,
pubmed-meshheading:17562315-Animals,
pubmed-meshheading:17562315-Binding Sites,
pubmed-meshheading:17562315-Catalysis,
pubmed-meshheading:17562315-Chondrodysplasia Punctata, Rhizomelic,
pubmed-meshheading:17562315-Conserved Sequence,
pubmed-meshheading:17562315-Crystallography, X-Ray,
pubmed-meshheading:17562315-Dictyostelium,
pubmed-meshheading:17562315-Dimerization,
pubmed-meshheading:17562315-Flavin-Adenine Dinucleotide,
pubmed-meshheading:17562315-Histidine,
pubmed-meshheading:17562315-Humans,
pubmed-meshheading:17562315-Hydrogen Bonding,
pubmed-meshheading:17562315-Lipid Metabolism, Inborn Errors,
pubmed-meshheading:17562315-Models, Biological,
pubmed-meshheading:17562315-Models, Chemical,
pubmed-meshheading:17562315-Models, Molecular,
pubmed-meshheading:17562315-Molecular Sequence Data,
pubmed-meshheading:17562315-Molecular Structure,
pubmed-meshheading:17562315-Peroxisomal Disorders,
pubmed-meshheading:17562315-Phenylalanine,
pubmed-meshheading:17562315-Phospholipid Ethers,
pubmed-meshheading:17562315-Protein Binding,
pubmed-meshheading:17562315-Protein Conformation,
pubmed-meshheading:17562315-Protein Structure, Secondary,
pubmed-meshheading:17562315-Protein Structure, Tertiary,
pubmed-meshheading:17562315-Recombinant Proteins,
pubmed-meshheading:17562315-Sequence Homology, Amino Acid,
pubmed-meshheading:17562315-Spectrum Analysis, Raman,
pubmed-meshheading:17562315-Substrate Specificity,
pubmed-meshheading:17562315-Tyrosine
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pubmed:year |
2007
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pubmed:articleTitle |
The crucial step in ether phospholipid biosynthesis: structural basis of a noncanonical reaction associated with a peroxisomal disorder.
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pubmed:affiliation |
Dipartimento di Genetica e Microbiologia, Università di Pavia, via Ferrata 1, 27100 Pavia, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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