Abstract
Recently, High Mobility Group Box1 (HMGB1) protein has been reported as an inflammatory cytokine present in all nucleated cells with crucial role in the genesis and promotion of cancer. No HMGB1 protein mice model and its active site details are available to validate mice in vivo experiments. Here, for the first time we have reported in silico mice HMGB1 model using human HMGB1 template. Prepared HMGB1 secondary structure showed 6-α helices, 5-β turns, 2-γ turns with 67% α-helices, 32% coil and 9% turn without β-sheet, and classified as α-class protein. Ramachandran plot analysis showed 98.2% and 92.3% residues lies in favoured region, verified by RAMPAGE and PDBsum server respectively. Cancer atlas of HMGB1 protein showed up-regulated expression of HMGB1 gene in different cancer, proved by CAB (CAB005873) and HPA-antibody (HPA003506) in silico. HMGB1 protein showed interaction with different biologically important inflammatory protein as depicted in STRING result.Prominent active site has residues Tyr78Ile79Pro80-81Lys82Gly83vGlu84Thr85Lys86-88Phe89Lys90Asp91Pro92Asn93Tyr162Lys165 with 310 Å3 site volume.Interacting residues of CGA-HMGB1 docked complex were ILE79PRO80-81LYS82GLY83GLU84LYS86-88PHE89Arg163Ala164LYS165Gly166 with docking score 3872 and surface area 412.6. CGA-conformer C3950 showed best docking than CGA and conformer-ZINC03947476, iso-chlorogenic acid and cischlorogenic acid. HMGB1 mice model could be a good therapeutic target for anti-cancerous drugs.
Highlights
Cancer is a foremost cause of global death and recently, High Mobility Group Box1 (HMGB1) has been recognized for inflammation related cancer genesis [1, 2]
We reported that chlorogenic acid (CGA) binds with the active site of HMGB1 as proved by molecular docking experiment, mitigating its activity and ability to cause cancer
The structural composition of mice HMGB1 protein model was confirmed by the PDBsum server (Figure 1b)
Summary
Cancer is a foremost cause of global death and recently, HMGB1 has been recognized for inflammation related cancer genesis [1, 2]. It is made up of three domains, A-box (N-terminal domain), Bbox (central domain) and terminal C-domain [3]. Active secretion of HMGB1 occurs from immune cells e.g. macrophages, monocytes, NK cells, while passive secretion occurs from damaged necrotic cells [1, 4]. It has extracellular activities as a cytokine, since mediates inflammation, proliferation and migration in different cancers [5]. The therapeutic molecule HMGB1 could be targeted by CGA-conformers or other biomolecules drugs to cure and prevent cancer, as our in silico data revealed
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