Linked Life Data

9480810

Source:http://linkedlifedata.com/resource/pubmed/id/9480810

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-3-27
pubmed:abstractText
Lecithin-cholesterol acyltransferase (LCAT) is responsible for the formation of cholesterol esters in plasma and is implicated in the removal of excess cholesterol from peripheral tissues. It is generally accepted that the catalytic mechanism of LCAT is similar to that of serine proteases and lipases involving a Ser, a His, and an acidic amino acid residue. Ser181 in LCAT has been previously identified as a catalytic residue; however, the active site His and acidic residue have not yet been identified. In this study we have used a variety of approaches to identify the putative active site histidine. Alignments of LCAT sequences across various species indicate that the four histidines at positions 180, 263, 368, and 377 are conserved and could be involved in catalysis. Based on the observation that the members of the triad preserve the same orientation in the primary sequence of a large number of lipases, we eliminated His180 as a potential candidate. Mutational analysis along with functional assays show that, in contrast to the replacement of His263 and His368, the replacement of the His at position 377 with Gly, Ala, or Ser obliterates LCAT activity with interfacial and water-soluble substrates, thus indicating a role of His377 in catalysis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
243
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
337-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Mutagenesis of highly conserved histidines in lecithincholesterol acyltransferase: identification of an essential histidine (His 377).
pubmed:affiliation
Department of Biochemistry, College of Medicine at Urbana-Champaign, University of Illinois 61801, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't