1g63

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File:1g63.gif


1g63, resolution 2.50Å

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PEPTIDYL-CYSTEINE DECARBOXYLASE EPID

OverviewOverview

Epidermin from Staphylococcus epidermidis Tu3298 is an antimicrobial peptide of the lantibiotic family that contains, amongst other unusual amino acids, S:-[(Z:)- 2-aminovinyl]-D-cysteine. This residue is introduced by post-translational modification of the ribosomally synthesized precursor EpiA. Modification starts with the oxidative decarboxylation of its C-terminal cysteine by the flavoprotein EpiD generating a reactive (Z:)-enethiol intermediate. We have determined the crystal structures of EpiD and EpiD H67N in complex with the substrate pentapeptide DSYTC at 2.5 A resolution. Rossmann-type monomers build up a dodecamer of 23 point symmetry with trimers disposed at the vertices of a tetrahedron. Oligomer formation is essential for binding of flavin mononucleotide and substrate, which is buried by an otherwise disordered substrate recognition clamp. A pocket for the tyrosine residue of the substrate peptide is formed by an induced fit mechanism. The substrate contacts flavin mononucleotide only via Cys-Sgamma, suggesting its oxidation as the initial step. A thioaldehyde intermediate could undergo spontaneous decarboxylation. The unusual substrate recognition mode and the type of chemical reaction performed provide insight into a novel family of flavoproteins.

About this StructureAbout this Structure

1G63 is a Single protein structure of sequence from Staphylococcus epidermidis with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the peptidyl-cysteine decarboxylase EpiD complexed with a pentapeptide substrate., Blaesse M, Kupke T, Huber R, Steinbacher S, EMBO J. 2000 Dec 1;19(23):6299-310. PMID:11101502

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