Unknown

Dataset Information

0

Crystal structure of the peptidyl-cysteine decarboxylase EpiD complexed with a pentapeptide substrate.


ABSTRACT: Epidermin from Staphylococcus epidermidis Tü3298 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.

SUBMITTER: Blaesse M 

PROVIDER: S-EPMC305864 | biostudies-literature | 2000 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Crystal structure of the peptidyl-cysteine decarboxylase EpiD complexed with a pentapeptide substrate.

Blaesse M M   Kupke T T   Huber R R   Steinbacher S S  

The EMBO journal 20001201 23


Epidermin from Staphylococcus epidermidis Tü3298 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  ...[more]

Similar Datasets

| S-EPMC2809104 | biostudies-literature
| S-EPMC3755991 | biostudies-literature
| S-EPMC2193177 | biostudies-literature
| S-EPMC4904194 | biostudies-literature
| S-EPMC2203289 | biostudies-literature
| S-EPMC5012210 | biostudies-literature
| S-EPMC1855892 | biostudies-literature
| S-EPMC2530905 | biostudies-literature
| S-EPMC5947705 | biostudies-literature
| S-EPMC7099390 | biostudies-literature