Linked Life Data

11325608

Source:http://linkedlifedata.com/resource/pubmed/id/11325608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-4-30
pubmed:databankReference
pubmed:abstractText
The list of diseases linked to defects in lipid metabolism has recently been augmented by the addition of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS: MIM 260920), which are correlated with depressed levels of mevalonate kinase activity [1,2] and protein [1]. More specifically, a V377I substitution has been proposed to account for this disease. We observed that V377 appears to be far from invariant in eukaryotic mevalonate kinases. Prokaryotic mevalonate kinases are lower in molecular weight and several terminate prior to residue 377 of the eukaryotic proteins. These observations prompted our direct test of the impact of V377 on activity and protein stability by engineering a V377I mutation in a recombinant human mevalonate kinase. The mutant protein has been isolated and kinetically characterized. In comparison with wild-type enzyme, V377I exhibits only modest differences (notably > or = 6-fold inflation of K(m(MVA))) that do not account for the diminished mevalonate kinase activity assayed in HIDS cell extracts. Moreover, thermal inactivation (50 degrees C) of isolated wild-type and V377I enzymes demonstrates little difference in stability between these proteins. We conclude that a single V377I substitution is unlikely to explain the observation of depressed mevalonate kinase stability and catalytic activity in HIDS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
1531
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
165-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Characterization of mevalonate kinase V377I, a mutant implicated in defective isoprenoid biosynthesis and HIDS/periodic fever syndrome.
pubmed:affiliation
Biochemistry Department, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.