3o24: Difference between revisions
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==Crystal structure of the brevianamide F prenyltransferase FtmPT1 from Aspergillus fumigatus== | |||
<StructureSection load='3o24' size='340' side='right' caption='[[3o24]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o24]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O24 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O24 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o2k|3o2k]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ftmPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=746128 Aspergillus fumigatus])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o24 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o24 RCSB], [http://www.ebi.ac.uk/pdbsum/3o24 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 alpha/beta-barrel fold, consisting of 10 circularly arranged beta-strands surrounded by alpha-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. | |||
Structure-Function Analysis of an Enzymatic Prenyl Transfer Reaction Identifies a Reaction Chamber with Modifiable Specificity.,Jost M, Zocher G, Tarcz S, Matuschek M, Xie X, Li SM, Stehle T J Am Chem Soc. 2010 Nov 24. PMID:21105662<ref>PMID:21105662</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aspergillus fumigatus]] | [[Category: Aspergillus fumigatus]] | ||
[[Category: Jost, M | [[Category: Jost, M]] | ||
[[Category: Stehle, T | [[Category: Stehle, T]] | ||
[[Category: Zocher, G E | [[Category: Zocher, G E]] | ||
[[Category: Brevianamide f prenyltransferase]] | [[Category: Brevianamide f prenyltransferase]] | ||
[[Category: Pt barrel]] | [[Category: Pt barrel]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||