Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme

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′-...

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Autores principales:	Rushikesh Patel, Ajay Kumar Raj, Kiran Bharat Lokhande, Mazen A. Almasri, Khalid J. Alzahrani, Asma Saleh Almeslet, K. Venkateswara Swamy, Gargi S. Sarode, Sachin C. Sarode, Shankargouda Patil, Nilesh Kumar Sharma
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	oral cancer metabolite biomarkers SAICAR pyruvate kinase M2 in silico studies Medicine R
Acceso en línea:	https://doaj.org/article/ecf7d501fbed4087aefe7433ad668fff
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spelling	oai:doaj.org-article:ecf7d501fbed4087aefe7433ad668fff2021-11-11T16:22:33ZDetection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme10.3390/ijerph1821112251660-46011661-7827https://doaj.org/article/ecf7d501fbed4087aefe7433ad668fff2021-10-01T00:00:00Zhttps://www.mdpi.com/1660-4601/18/21/11225https://doaj.org/toc/1661-7827https://doaj.org/toc/1660-4601Oncometabolites 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.Rushikesh PatelAjay Kumar RajKiran Bharat LokhandeMazen A. AlmasriKhalid J. AlzahraniAsma Saleh AlmesletK. Venkateswara SwamyGargi S. SarodeSachin C. SarodeShankargouda PatilNilesh Kumar SharmaMDPI AGarticleoral cancermetabolite biomarkersSAICARpyruvate kinase M2in silico studiesMedicineRENInternational Journal of Environmental Research and Public Health, Vol 18, Iss 11225, p 11225 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral cancer metabolite biomarkers SAICAR pyruvate kinase M2 in silico studies Medicine R
spellingShingle	oral cancer metabolite biomarkers SAICAR pyruvate kinase M2 in silico studies Medicine R Rushikesh Patel Ajay Kumar Raj Kiran Bharat Lokhande Mazen A. Almasri Khalid J. Alzahrani Asma Saleh Almeslet K. Venkateswara Swamy Gargi S. Sarode Sachin C. Sarode Shankargouda Patil Nilesh Kumar Sharma Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme
description	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.
format	article
author	Rushikesh Patel Ajay Kumar Raj Kiran Bharat Lokhande Mazen A. Almasri Khalid J. Alzahrani Asma Saleh Almeslet K. Venkateswara Swamy Gargi S. Sarode Sachin C. Sarode Shankargouda Patil Nilesh Kumar Sharma
author_facet	Rushikesh Patel Ajay Kumar Raj Kiran Bharat Lokhande Mazen A. Almasri Khalid J. Alzahrani Asma Saleh Almeslet K. Venkateswara Swamy Gargi S. Sarode Sachin C. Sarode Shankargouda Patil Nilesh Kumar Sharma
author_sort	Rushikesh Patel
title	Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme
title_short	Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme
title_full	Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme
title_fullStr	Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme
title_full_unstemmed	Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme
title_sort	detection of nail oncometabolite saicar in oral cancer patients and its molecular interactions with pkm2 enzyme
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ecf7d501fbed4087aefe7433ad668fff
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Detection of Nail Oncometabolite SAICAR in Oral Cancer Patients and Its Molecular Interactions with PKM2 Enzyme

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