1mvn: Difference between revisions

[[Image:1mvn.gif|left|200px]]<br /><applet load="1mvn" size="350" color="white" frame="true" align="right" spinBox="true"  

The Arabidopsis thaliana protein AtHAL3a decarboxylates 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine, a step in coenzyme A biosynthesis. Surprisingly, this decarboxylation reaction is carried out as an FMN-dependent redox reaction. In the first half-reaction, the side-chain of the cysteine residue of 4'-phosphopantothenoylcysteine is oxidised and the thioaldehyde intermediate decarboxylates spontaneously to the 4'-phosphopantothenoyl-aminoethenethiol intermediate. In the second half-reaction this compound is reduced to 4'-phosphopantetheine and the FMNH(2) cofactor is re-oxidised. The active site mutant C175S is unable to perform this reductive half-reaction. Here, we present the crystal structure of the AtHAL3a mutant C175S in complex with the reaction intermediate pantothenoyl-aminoethenethiol and FMNH(2). The geometry of binding suggests that reduction of the C(alpha)=C(beta) double bond of the intermediate can be performed by direct hydride-transfer from N5 of FMNH(2) to C(beta) of the aminoethenethiol-moiety supported by a protonation of C(alpha) by Cys175. The binding mode of the substrate is very similar to that previously observed for a pentapeptide to the homologous enzyme EpiD that introduces the aminoethenethiol-moiety as final reaction product at the C terminus of peptidyl-cysteine residues. This finding further supports our view that these homologous enzymes form a protein family of homo-oligomeric flavin-containing cysteine decarboxylases, which we have termed HFCD family.

1MVN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana] with <scene name='pdbligand=PCO:'>PCO</scene> and <scene name='pdbligand=FMN:'>FMN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphopantothenoylcysteine_decarboxylase Phosphopantothenoylcysteine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.36 4.1.1.36] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MVN OCA].  

[[Category: Culianez-Macia, F A.]]

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