Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India.
Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411033, Maharashtra, India.
Int J Environ Res Public Health. 2021 Oct 26;18(21):11225. doi: 10.3390/ijerph182111225.
Oncometabolites are known to drive metabolic adaptations in oral cancer. Several oncometabolites are known to be shared between cancer cells and non-cancer cells including microbiotas to modulate the tumor microenvironment. Among potential oncometabolites, succinylaminoimidazolecarboxamide ribose5'-phosphate (SAICAR) supports the growth and invasiveness of cancer cells by pyruvate kinase M2 (PKM2) enzyme in a glucose starved tumor microenvironment. There is a significant gap that shows the detection of SAICAR in biological samples including nails of oral cancer patients. Metabolite identification of SAICAR was investigated in the nails of oral cancer patients using novel vertical tube gel electrophoresis (VTGE) and LC-HRMS. Further molecular docking and molecular dynamics simulations (MDS) were employed to determine the nature of molecular interactions of SAICAR (CHEBI ID:18319) with PKM2 (PDB ID: 4G1N). Molecular docking of SAICAR (CHEBI ID:18319) was performed against pyruvate kinase M2 (PDB ID: 4G1N). Data suggest the presence of oncometabolite SAICAR in nails of oral cancer. Molecular docking of SAICAR with PKM2 showed appreciable binding affinity (-8.0 kcal/mol) with residues including ASP407, THR405, GLU410, ARG443, GLY321, ARG436, HIS439, LYS266, and TYR466. Furthermore, MDS confirmed the specific binding of SAICAR within the activator site of PKM2 and the stability of SAICAR and PKM2 molecular interactions. In conclusion, SAICAR is a promising oncometabolite biomarker present in the nails of oral cancer patients. A significant activation potential of SAICAR exists with the PKM2 enzyme.
代谢物被认为可驱动口腔癌中的代谢适应。几种代谢物被认为在癌细胞和非癌细胞（包括微生物群）之间共享，以调节肿瘤微环境。在潜在的代谢物中，琥珀酰氨基咪唑羧酰胺核糖 5′-磷酸（SAICAR）通过在葡萄糖饥饿的肿瘤微环境中的丙酮酸激酶 M2（PKM2）酶支持癌细胞的生长和侵袭性。有一个显著的差距表明，在包括口腔癌患者指甲在内的生物样本中检测到 SAICAR。使用新型垂直管凝胶电泳（VTGE）和 LC-HRMS 研究了 SAICAR 在口腔癌患者指甲中的代谢产物鉴定。进一步进行了分子对接和分子动力学模拟（MDS），以确定 SAICAR（ CHEBI ID：18319）与 PKM2（PDB ID：4G1N）的分子相互作用的性质。对 SAICAR（ CHEBI ID：18319）进行了分子对接，以对抗丙酮酸激酶 M2（PDB ID：4G1N）。数据表明，口腔癌患者指甲中存在代谢物 SAICAR。SAICAR 与 PKM2 的分子对接显示与包括 ASP407、THR405、GLU410、ARG443、GLY321、ARG436、HIS439、LYS266 和 TYR466 在内的残基具有可观的结合亲和力（-8.0 kcal/mol）。此外，MDS 证实了 SAICAR 在 PKM2 的激活位点内的特异性结合以及 SAICAR 和 PKM2 分子相互作用的稳定性。总之，SAICAR 是一种有前途的代谢物生物标志物，存在于口腔癌患者的指甲中。SAICAR 与 PKM2 酶存在显著的激活潜力。
