Linked Life Data

11781309

Source:http://linkedlifedata.com/resource/pubmed/id/11781309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2002-3-18
pubmed:abstractText
It was recently demonstrated that mutations in the human SPTLC1 gene, encoding the Lcb1p subunit of serine palmitoyltransferase (SPT), cause hereditary sensory neuropathy type I . As a member of the subfamily of pyridoxal 5'-phosphate enzymes known as the alpha-oxoamine synthases, serine palmitoyltransferase catalyzes the committed step of sphingolipid synthesis. The residues that are mutated to cause hereditary sensory neuropathy type I reside in a highly conserved region of Lcb1p that is predicted to be a catalytic domain of Lcb1p on the basis of alignments with other members of the alpha-oxoamine synthase family. We found that the corresponding mutations in the LCB1 gene of Saccharomyces cerevisiae reduce serine palmitoyltransferase activity. These mutations are dominant and decrease serine palmitoyltransferase activity by 50% when the wild-type and mutant LCB1 alleles are coexpressed. We also show that serine palmitoyltransferase is an Lcb1p small middle dotLcb2p heterodimer and that the mutated Lcb1p proteins retain their ability to interact with Lcb2p. Modeling studies suggest that serine palmitoyltransferase is likely to have a single active site that lies at the Lcb1p small middle dotLcb2p interface and that the mutations in Lcb1p reside near the lysine in Lcb2p that is expected to form the Schiff's base with the pyridoxal 5'-phosphate cofactor. Furthermore, mutations in this lysine and in a histidine residue that is also predicted to be important for pyridoxal 5'-phosphate binding to Lcb2p also dominantly inactivate SPT similar to the hereditary sensory neuropathy type 1-like mutations in Lcb1p.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10194-200
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11781309-Acyltransferases, pubmed-meshheading:11781309-Alleles, pubmed-meshheading:11781309-Amino Acid Sequence, pubmed-meshheading:11781309-Binding Sites, pubmed-meshheading:11781309-Blotting, Western, pubmed-meshheading:11781309-Calcium, pubmed-meshheading:11781309-Catalysis, pubmed-meshheading:11781309-Chromatography, Liquid, pubmed-meshheading:11781309-Dimerization, pubmed-meshheading:11781309-Diploidy, pubmed-meshheading:11781309-Hereditary Sensory and Autonomic Neuropathies, pubmed-meshheading:11781309-Histidine, pubmed-meshheading:11781309-Lysine, pubmed-meshheading:11781309-Microsomes, Liver, pubmed-meshheading:11781309-Models, Chemical, pubmed-meshheading:11781309-Models, Molecular, pubmed-meshheading:11781309-Molecular Sequence Data, pubmed-meshheading:11781309-Mutagenesis, Site-Directed, pubmed-meshheading:11781309-Mutation, pubmed-meshheading:11781309-Plasmids, pubmed-meshheading:11781309-Precipitin Tests, pubmed-meshheading:11781309-Protein Binding, pubmed-meshheading:11781309-Protein Structure, Tertiary, pubmed-meshheading:11781309-Saccharomyces cerevisiae, pubmed-meshheading:11781309-Saccharomyces cerevisiae Proteins, pubmed-meshheading:11781309-Sequence Homology, Amino Acid, pubmed-meshheading:11781309-Serine C-Palmitoyltransferase, pubmed-meshheading:11781309-Sphingolipids
pubmed:year
2002
pubmed:articleTitle
Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20184, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.