Linked Life Data

7582974

Source:http://linkedlifedata.com/resource/pubmed/id/7582974

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1995-12-28
pubmed:abstractText
In an effort to better understand the favorable binding interactions between the reversible picomolar inhibitor 3-(4-benzyloxyphenyl)-2-(R)-amino-1- propanethiol (1) and leukotriene A4 (LTA4) hydrolase (EC 3.3.2.6), we prepared a number of derivatives of 1-L and other related structures, and assayed their inhibition of LTA4 hydrolase-catalyzed hydrolysis of L-alanine-p-nitroanilide. The inhibition data was analyzed using a weighted non-linear least-squares curve fitting computer program developed for this purpose to fit data derived under the non-Michaelis-Menten condition of [I]t < [E]t. The free thiol is necessary for sub-micromolar binding and the enzyme prefers the R enantiomer over the S enantiomer, in contrast to the stereoselectivity displayed towards bestatin, an inhibitor of somewhat similar structure. Substitution of acid moieties around the periphery of the benzyloxyphenyl portion of 1-L leads to substantially decreased binding, suggesting that this group resides within a large hydrophobic pocket when bound to the enzyme. Possible LTA4 binding modes in the active site of LTA4 hydrolase, including a possible direct role for the carboxylic acid of LTA4 in the enzyme-catalyzed hydrolysis of leukotriene A4, are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
969-95
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Investigation of the inhibition of leukotriene A4 hydrolase.
pubmed:affiliation
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't