Catharanthus roseus (C. roseus) is an important medicinal plant used to treat various diseases. The plant is distributed throughout the world. It is known to produce modern chemotherapeutic agent for pain-relieving properties . One of the important types of alkaloid is the vinblastine produced from C. roseus which was reported due to its antitumor activity and has wide pharmaceutical use . It has been reported that accumulation of free radicals can cause pathological conditions such as ischemia, asthma, arthritis, inflammation, neurodegeneration, Parkinson’s diseases, mongolism, aging process, and perhaps dementia . The flower petals, seeds, and other parts of Catharanthus roseus exhibit antioxidant properties. Thus, phenolic compounds have redox properties that act as reducing agents, hydrogen donors, singlet oxygen quenchers, or metal chelator.
C. roseus was of enormous pharmaceutical interest because it contains more than 120 terpenoid indole alkaloids (TIAs). Terpenoid indole alkaloids (TIAs) are among the most important secondary metabolites in plants that play important roles in the growth and reproductive development of plants . Over 100 different TIAs were discovered in Catharanthus roseus (periwinkle) . Strictosidine was found to be the key biosynthetic precursor of TIA. It was presented in a wide variety of higher plants . This important molecule is generated by strictosidine synthase (STR) from tryptamine and secologanin and catalyzes the synthesis of 3-a(S)-strictosidine. STR 1 is the first STR gene isolated from Rauvolfia serpentina. STR1 catalyzes the Pictet-Spengler reaction between tryptamine and secologanin and is a key enzyme for the biosynthesis of alkaloids [7, 8]. The Pictet-Spengler reaction was a two-part reaction. First, an electron-rich aromatic amine and an aldehyde condense to form an iminium species. Second, an electrophilic aromatic substitution reaction occurs in which the aryl amine attacks the electrophilic iminium to yield a positively charged intermediate which is then deprotonated to yield the β-carboline product(s). In nonenzymatically catalyzed reactions, two enantiomers are typically formed, but strictosidine synthase catalyzes the asymmetric synthesis of the strictosidine 3 diastereomer .
This was the central reaction in the biosynthesis of the entire family of monoterpenoid indole alkaloids in plants that includes vincamine, ajmaline, raubasine, quinine, vinblastine, reserpine, vincamine, C-toxiferen I, and camptothesine. STR proteins are involved in different physiological and biochemical pathways. The monoterpenoid-derived indole alkaloids were one of the structurally largest and pharmacologically most diverse alkaloid families in higher plants. These alkaloids have medical applications and therapeutics include the treatment of cancer (vinblastine or the camptothecin-derivative topotecan), malaria (quinine), hypertension (raubasine and reserpine), schizophrenia (reserpine in high dosage), disturbed cerebral blood flow (vincamine), and antiarrhythmic heart disorders (ajmaline), from the Indian medicinal plant Rauvolfia serpentina .
The major drawbacks of experimental mehod used to charecterize protein was involvement of high cost and time consumption. Thus, these methods were not amenable to high throughput techniques. In silico approaches provide a viable solution to these problems. Computational tools provide researchers to understand physicochemical and structural properties of proteins. The amino acid sequence provides most of the information required for determining and characterizing the molecule’s function and physical and chemical properties. In this study, the in silico analysis and homology modeling studies on STR involved in alkaloid biosynthesis was reported. The three-dimensional structure for this protein was yet not available. Hence to describe its structural features and to understand molecular function, the model structures for this protein was constructed. Physicochemical characterization was performed by computing theoretical isoelectric point (pI), molecular weight, total number of positive and negative residues, extinction coefficient, instability index, aliphatic index, and grand average hydropathy (GRAVY). Functional analysis and secondary structure prediction of these proteins was performed by SOSUI server and SOPMA, respectively. The modeling of the three-dimensional structure of the proteins was performed by Swiss model. The model was validated using protein structure checking tools PROCHECK and PROVE.