Linked Life Data

21105662

Source:http://linkedlifedata.com/resource/pubmed/id/21105662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2010-12-15
pubmed:abstractText
Fungal indole prenyltransferases participate in a multitude of biosynthetic pathways. Their ability to prenylate diverse substrates has attracted interest for potential use in chemoenzymatic synthesis. The fungal indole prenyltransferase FtmPT1 catalyzes the prenylation of brevianamide F in the biosynthesis of fumitremorgin-type alkaloids, which show diverse pharmacological activities and are promising candidates for the development of antitumor agents. Here, we report crystal structures of unliganded Aspergillus fumigatus FtmPT1 as well as of a ternary complex of FtmPT1 bound to brevianamide F and an analogue of its isoprenoid substrate dimethylallyl diphosphate. FtmPT1 assumes a rare ?/?-barrel fold, consisting of 10 circularly arranged ?-strands surrounded by ?-helices. Catalysis is performed in a hydrophobic reaction chamber at the center of the barrel. In combination with mutagenesis experiments, our analysis of the liganded and unliganded structures provides insight into the mechanism of catalysis and the determinants of regiospecificity. Sequence conservation of key features indicates that all fungal indole prenyltransferases possess similar active site architectures. However, while the dimethylallyl diphosphate binding site is strictly conserved in these enzymes, subtle changes in the reaction chamber likely allow for the accommodation of diverse aromatic substrates for prenylation. In support of this concept, we were able to redirect the regioselectivity of FtmPT1 by a single mutation of glycine 115 to threonine. This finding provides support for a potential use of fungal indole prenyltransferases as modifiable bioreactors that can be engineered to catalyze highly specific prenyl transfer reactions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-5126
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17849-58
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Structure-function analysis of an enzymatic prenyl transfer reaction identifies a reaction chamber with modifiable specificity.
pubmed:affiliation
Interfakulta?res Institut fu?r Biochemie, Universita?t Tu?bingen, Hoppe-Seyler-Strasse 4, 72076 Tu?bingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't