EC Number   |
General Information |
Reference |
|---|
  1.3.99.36 | evolution |
CypD possesses a structural fold highly similar to two structurally characterized LanDs (EpiD in epidermin biosynthesis and MrsD in mersacidin biosynthesis). Similar to CypD, the substrate binding clamps are also not observed in the crystal structures of EpiD and MrsD when the peptide substrate is absent. But because CypD shares no detectable sequence similarity with these two LanDs, this finding reveals a convergent evolution in AviCys biosynthesis |
-, 763314 |
| 1.3.99.36 | evolution |
flavin-dependent Cys decarboxylases are highly divergent among different RiPP classes. Cys decarboxylases from four RiPP classes have evolved independently and form two major clusters. Convergent evolution of AviCys biosynthesis, all the flavin-dependent Cys decarboxylases likely have a similar Rossmann fold despite their sequence divergences. Evolution of Cys decarboxylases involved in AviCys biosynthesis, overview |
-, 763030 |
| 1.3.99.36 | more |
because only the C-terminal three residues of CypA are essential for CypD recognition, biochemical analyses in this study were performed by using synthetic oligopeptides. Since the C-terminal sequence of CypA is highly hydrophobic, we synthesized peptide 1 (KKSTISLVC) and peptide 2 (KKSTICLVC), which are similar to the CypA C-terminus but contain two Lys residues in the N-termini, to increase aqueous solubility and hence the reaction efficiency. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS) analysis of each reaction mixture clearly show that both peptides are decarboxylated by CypD, suggesting that the two N-terminal Lys residues do not interfere with CypD activity |
-, 763536 |
| 1.3.99.36 | more |
movements of the substrate-binding clamp of cypemycin decarboxylase CypD, mechanism, substrate-induced secondary structure change in CypD, overview. The substrate binding clamp of CypD undergoes dramatic fluctuation. Structure and motion of the missing region by performing 3 × 300 ns unbiased molecular dynamics (MD) analysis, and principle component analysis (PCA) is utilized to analyze the protein backbone motion in MD trajectory. The substrate binding clamp of CypD undergoes dramatic fluctuation, mediating both the substrate entrance into and product release from the catalytic pocket. Extensive molecular dynamic simulations and Fourier transform IR analyses indicate that binding of the substrate induces substantial structural change of the enzyme, converting the substrate-binding clamp from a random loop to a more ordered structure comprising two beta sheets and a beta turn. The salt bridge between Arg159 guanine and the Cys carboxylate of substrate plays an important role in mediating substrate binding, while hydrophobic interactions are also important in this process. Computational construction of a CypD-substrate complex and interaction analysis. The carboxyl group of substrate forms a salt bridge with the guanine moiety of Arg159 and also hydrogen bonds with the amide NH of Ala160 and Ser161. A hydrogen bond is also found between the Val158 C=O and the penultimate amide NH in the C-terminus. The substrate also interacts with several residues (e.g. Leu23, Trp26, Trp27, Val155, Val168) via hydrophobic interactions |
-, 763314 |
| 1.3.99.36 | more |
structure-function analysis, LC-HR-MS analysis, overview |
-, 763750 |
| 1.3.99.36 | physiological function |
linaridins are a small but growing class of natural products belonging to the ribosomally synthesized and posttranslationally modified peptide (RiPP) superfamily. The class A linaridins, exemplified by cypemycin, possess an unusual S-[(Z)-2-aminovinyl]-D-cysteine (AviCys) residue. Formation of the AviCys in cypemycin requires an oxidative decarboxylation of the precursor peptide C-terminal Cys, and this reaction is catalyzed by a flavin-dependent decarboxylase CypD. Analysis of the molecular recognition processes of CypD by a combination of computational and biochemical analysis, overview |
-, 763314 |
| 1.3.99.36 | physiological function |
ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products that exist in all three domains of life and possess diverse biological activities. -RiPPs are derived from a ribosomally synthesized precursor peptide, which, in most cases, consists of an N-terminal region (leader peptide) that is essential for the recognition by post-translationally modifying enzymes, and a C-terminal region (core peptide) that is finally transformed to the mature product. A unique RiPP structural motif is S-[(Z)-2-aminovinyl]-D-cysteine (AviCys) has been found in several classes of RiPPs. Cypemycin decarboxylase (CypD) catalyzes the the AviCys formation. In cypemycin biosynthesis, Dha formation is prior to decarboxylation of the C-terminal Cys. AviCys is structurally similar to lanthionine, a characteristic motif that defines lanthipeptides (lanthionine-containing peptides). Cypemycin decarboxylase CypD is not responsible for aminovinyl-cysteine (AviCys) ring formation. AviCys formation does not require a specific cyclase. It is proposed that the AviCys motif may be produced enzymatically by feeding the Dha-containing peptide substrate to the corresponding decarboxylase. Cypemycin is a prototypical member of the linaridin family, which is defined as linear dehydrated (arid) peptides. CypD alone is unable to form the AviCys ring. Production of Dha from the CypA Cys19 is likely prior to the CypD-catalyzed decarboxylation of Cys22 |
-, 763536 |
| 1.3.99.36 | physiological function |
S-[(Z)-2-aminovinyl]-D-cysteine (AviCys) is a unique motif found in several classes of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Biosynthesis of AviCys requires flavin-dependent Cys decarboxylases, which are highly divergent among different RiPP classes |
-, 763030 |
