Molecular and structural basis of metabolic diversity mediated by prenyldiphosphate converting enzymes.

摘要: General thermodynamic calculations using the semiempiric PM3 method have led to conclusion that prenyldiphosphate converting enzymes require at least one divalent metal cation for activation and cleavage of diphosphate-prenyl ester bond, or they must provide structural elements efficient stabilization intermediate prenyl cation. The most important common features, which guide product specificity in both terpene synthases aromatic transferases are amino acid side chains, stabilize cations by cation-pi interactions. In case transferases, a proton abstraction from phenolic hydroxyl group second substrate will enhance electron density ortho-position initial prenylation compound usually occurs. A model structure integral transmembrane-bound transferase UbiA was developed, currently represents first insight into this prenylating with fold different other transferases. Based on model, structure-activity relationships mechanistic aspects related proteins, example those Lithospermum erythrorhizon enzyme AuaA Stigmatella aurantiaca involved aurachin biosynthesis, were elucidated. high similarity prenyltransferases 5-epi-aristolochene synthase is an indication evolutionary relationship (cyclases). This further supported conserved DxxxD motif found protein families. contrast, there no such ABBA-fold, as NphB, any known family enzymes. Therefore, it possible these two groups might ancestors.