The Cystathionine β-Synthase enzyme catalyses the condensation of homocysteine with serine (canonical activity) to form cystathionine in the transsulfuration pathway. It also catalyses condensation of homocysteine with cysteine and forms cystathionine and H2S in alternative pathway. A homodimeric or oligomeric form of hCBS is obtained from the resolved crystal structure. Each sub-unit of hCBS is ∼551 amino acid (aa) residues long and it consists of Nterminal domain (1-70 aa), catalytic domain (71-386 aa) and C-terminal domain (386-551 aa). The hCBS is the only known pyridoxal 5-phosphate (PLP) dependent enzyme that also contains a Heme cofactor in the N-terminal domain. The iron of b-type hexacoordinated Heme in hCBS is axially coordinated with Cys52 (S -) and His65 (Nϵ2) aa residues (fig. ). In the catalytic domain, PLP forms internal aldimine with Lys119. Heme and PLP are connected by an α-helix 8. Although, the catalytic center PLP is distantly located ∼20 Å from the Heme site, disturbance in the Heme environment affects the hCBS enzymatic activity. Addition of a nucleophile to the electrophilic C4A atom of the Schiff base formed between PLP and Lys119 is the heart of enzymatic activity of PLP in CBS enzyme (fig. ). Intra-molecular proton transfer from phenolic -OH to C --N leads to tautomer shift to enzymatically active ketoenamine form in PLP, is associated with the change in π-electron configuration of PLP. An intermolecular hydrogen bond between phenolic oxygen (O -) and Asn149( -NH2) stabilise the Ketoenamine tautomer of the PLP, provided the αhelix 8 and Heme are kept intact. Change in the ligand environment around Heme iron, mutation in Arg266 residue leads to diminished enzymatic activity. The hydrogen bond interaction between Arg266 of the α-helix 8 and Cys52 of Heme has been extensively studied in our previous work. On the other hand, the disruption of the hydrogen bond present between Thr257 and Thr260 aa residues of the α-helix 8 and phosphate group of PLP also results in loss of enzymatic activity. Thus, being extended between Heme and PLP sites, the α-helix 8 acts as signal transactor between them. These two hydrogen bonding interactions pave a probable route for a bidirectional communication between those two sites. It is well established in the literature that the secondary structures of the α-helix mediates a numerous electron transfer processes in the biological systems including photoinduced charge transfer and electron transport in biological redox reactions. These features of the α-helical peptides make them the potential candidates for fabricating bio-inspired molecular junction based devices. In this work, we have tried to obtain a quantum mechanical description of the possible communication present in hCBS along with the exact contribution of the αhelix 8 towards the electronic modifications facilitating the communication. In order to understand the long-range electronic communications between the Heme and PLP through the α-helix 8, here we have adopted density functional theory based calculations to investigate a suitable model for α-helix 8 system tailored from a X-ray crystallographic geometry, reported by Mccorvie et al. with PDB id 4COO. The model communication pathway consists of three main components; i.e. hexacoordinated Heme (Heme), α-helix 8 and PLP. Out of 16 aa residues (TGGTITGIARKLKEKC) of the α-helix 8, 10 aa (TGGTITGIAR) residues are considered in the model for α-helix 8. The PLP model consists of the Schiff base formed between PLP and Lys119 (see SI 1.1 for details). As absorption and fluorescence spectroscopic techniques are widely used as a monitoring tool for studying hCBS related chemical phenomenon, we used simulated absorption spectra to understand the consequences of the electron-delocalization through the electron communication channels towards the frontier molecular orbitals. Range separated hybrid functional CAM-B3LYP 25 with def2-TZVP 26 basis set is used to study the ground state electronic structure of the modelled communication network. The same functional and basis set are also used to compute the absorption spectra within the simplified time dependent DFT (sTD-DFT) framework. The sTD-DFT has been proven to be quite effective method to study the photo-induced electron transfer processes in biological systems All the calculations are performed with ORCA 4.0 29 quantum chemistry code.