Linked Life Data

10496068

Source:http://linkedlifedata.com/resource/pubmed/id/10496068

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-10-20
pubmed:abstractText
The protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) can initiate the repair of age-damaged aspartyl and asparaginyl residues of intracellular proteins. The human gene PCMT1 encoding this enzyme has at least four polymorphic sites, one of which results in two major isoforms with either an Ile residue or a Val residue at amino acid position 119. The frequencies of the alleles encoding the Ile119 and Val119 variants are similar in Caucasian populations, but a predominance of the Ile119 allele exists in Asian and African populations. Analyses of the enzymatic activities of the Ile119 and Val119 variants in red blood cell lysates show that the higher specific activity and thermostability of the Ile119 isoform is balanced by the potentially compensating higher substrate affinity of the Val119 isoform. In a preliminary attempt to find an association between genotype frequency at the PCMT1 locus and healthy aging, we compared the distribution of genotypes in a healthy older population of Ashkenazi Jewish individuals with that in a younger ethnically matched control group. We found that 65% of the healthy older population had the heterozygous genotype, greater than the 50% expected by Hardy-Weinberg equilibrium, suggesting a possible selection for having both alleles of the repair methyltransferase in successful aging. Three additional polymorphisms in noncoding regions of the methyltransferase gene were found to be biallelic and demonstrated nonrandom association in a specific haplotype with the codon 119 polymorphism. Finally, we also detected a heterozygous mutation in the splicing branch site of intron 2 that did not appear to affect activity. This study will help define the normal physiological range of activity for this repair methyltransferase and give us a better understanding of its role in the processes of aging and disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1434-5161
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
275-88
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10496068-African Continental Ancestry Group, pubmed-meshheading:10496068-Aging, pubmed-meshheading:10496068-Amino Acid Sequence, pubmed-meshheading:10496068-Asian Continental Ancestry Group, pubmed-meshheading:10496068-Base Sequence, pubmed-meshheading:10496068-Consensus Sequence, pubmed-meshheading:10496068-European Continental Ancestry Group, pubmed-meshheading:10496068-Female, pubmed-meshheading:10496068-Genetic Variation, pubmed-meshheading:10496068-Humans, pubmed-meshheading:10496068-Isoenzymes, pubmed-meshheading:10496068-Isoleucine, pubmed-meshheading:10496068-Jews, pubmed-meshheading:10496068-Kinetics, pubmed-meshheading:10496068-Korea, pubmed-meshheading:10496068-Los Angeles, pubmed-meshheading:10496068-Male, pubmed-meshheading:10496068-Molecular Sequence Data, pubmed-meshheading:10496068-Norway, pubmed-meshheading:10496068-Pedigree, pubmed-meshheading:10496068-Polymorphism, Genetic, pubmed-meshheading:10496068-Protein D-Aspartate-L-Isoaspartate Methyltransferase, pubmed-meshheading:10496068-Protein Methyltransferases, pubmed-meshheading:10496068-Substrate Specificity, pubmed-meshheading:10496068-Valine
pubmed:year
1999
pubmed:articleTitle
Polymorphic forms of the protein L-isoaspartate (D-aspartate) O-methyltransferase involved in the repair of age-damaged proteins.
pubmed:affiliation
Molecular Biology Institute, University of California, Los Angeles, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't