title: Structural comparison, substrate specificity, and inhibitor binding of AGPase small subunit from monocot and dicot: present insight and future potential.
abstract: ADP-glucose pyrophosphorylase (AGPase) is the first rate limiting enzyme of starch biosynthesis pathway and has been exploited as the target for greater starch yield in several plants. The structure-function analysis and substrate binding specificity of AGPase have provided enormous potential for understanding the role of specific amino acid or motifs responsible for allosteric regulation and catalytic mechanisms, which facilitate the engineering of AGPases. We report the three-dimensional structure, substrate, and inhibitor binding specificity of AGPase small subunit from different monocot and dicot crop plants. Both monocot and dicot subunits were found to exploit similar interactions with the substrate and inhibitor molecule as in the case of their closest homologue potato tuber AGPase small subunit. Comparative sequence and structural analysis followed by molecular docking and electrostatic surface potential analysis reveal that rearrangements of secondary structure elements, substrate, and inhibitor binding residues are strongly conserved and follow common folding pattern and orientation within monocot and dicot displaying a similar mode of allosteric regulation and catalytic mechanism. The results from this study along with site-directed mutagenesis complemented by molecular dynamics simulation will shed more light on increasing the starch content of crop plants to ensure the food security worldwide.
authors.affiliation: Agri-Bioinformatics Promotion Programme, Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam 785013, India ; Department of Life Science & Bioinformatics, Assam University, Silchar, Assam 788011, India.
authors.forename: Kishore
authors.identifier: 0000-0002-1792-1522
authors.initials: K
authors.lastname: Sarma
authors.affiliation: Agri-Bioinformatics Promotion Programme, Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam 785013, India.
authors.forename: Priyabrata
authors.identifier: 0000-0001-9250-9362
authors.initials: P
authors.lastname: Sen
authors.affiliation: Agri-Bioinformatics Promotion Programme, Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam 785013, India.
authors.forename: Madhumita
authors.identifier: 0000-0002-3768-5336
authors.initials: M
authors.lastname: Barooah
authors.affiliation: Department of Life Science & Bioinformatics, Assam University, Silchar, Assam 788011, India.
authors.forename: Manabendra D
authors.initials: MD
authors.lastname: Choudhury
authors.affiliation: Department of Life Science & Bioinformatics, Assam University, Silchar, Assam 788011, India.
authors.forename: Shubhadeep
authors.identifier: 0000-0003-4174-1852
authors.initials: S
authors.lastname: Roychoudhury
authors.affiliation: Agri-Bioinformatics Promotion Programme, Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat, Assam 785013, India.
authors.forename: Mahendra K
authors.initials: MK
authors.lastname: Modi
mesh_terms: D000595:Amino Acid Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051599:Glucose-1-Phosphate Adenylyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D019684:Magnoliopsida / Q000201:enzymology*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D006109:Poaceae / Q000201:enzymology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D055672:Static Electricity; D040681:Structural Homology, Protein; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D021122:Protein Subunits; D051599:Glucose-1-Phosphate Adenylyltransferase