Linked Life Data

16242657

Source:http://linkedlifedata.com/resource/pubmed/id/16242657

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-10-24
pubmed:abstractText
A system is reported for the recombinant expression of individual ketoreductase (KR) domains from modular polyketide synthases (PKSs) and scrutiny of their intrinsic specificity and stereospecificity toward surrogate diketide substrates. The eryKR(1) and the tylKR(1) domains, derived from the first extension module of the erythromycin PKS and the tylosin PKS, respectively, both catalyzed reduction of (2R, S)-2-methyl-3-oxopentanoic acid N-acetylcysteamine thioester, with complete stereoselectivity and stereospecificity, even though the substrate is not tethered to an acyl carrier protein or an intact PKS multienzyme. In contrast, and to varying degrees, the isolated enzymes eryKR(2), eryKR(5), and eryKR(6) exercised poorer control over substrate selection and the stereochemical course of ketoreduction. These data, together with modeling of diketide binding to KR(1) and KR(2), demonstrate the fine energetic balance between alternative modes of presentation of ketoacylthioester substrates to KR active sites.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1074-5521
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1145-53
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Molecular basis of Celmer's rules: stereochemistry of catalysis by isolated ketoreductase domains from modular polyketide synthases.
pubmed:affiliation
Department of Biochemistry, University of Cambridge, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't