Investigation of the three-dimensional structure and interaction mechanism of poly (ADP-ribose) polymerase 4

• Main Authors: Ayhan Ünlü, Bircan Dinç
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2020-01-01
• Series: Biotechnology & Biotechnological Equipment
• Subjects: adp-ribosylating toxins; poly adp-ribose polymerases; nicotinamide adenine dinucleotide (nad); protein-ligand interaction
• Online Access: http://dx.doi.org/10.1080/13102818.2020.1726208

Poly ADP-ribose polymerases (PARPs) are family of proteins that use nicotinamide adenine dinucleotide (NAD) as substrate. Seventeen putative PARP sequences were determined in the human genome. Although PARPs show a variety of functions and low sequence identities, they share common structural and functional properties. In our study, PARP1 and PARP2 and PARP4 sequences in different species were compared; it was found that active sites of PARP1 for human, rat and mouse have highly conserved sequence. Overall folding of PARP1, PARP2 and PARP4 confirms similarity in catalytic domains but can differ in substrate proteins. The three-dimensional structure of PARP4 was interacted with NAD using the molecular docking method and the interaction sites were determined. When we modeled the three-dimensional structure of PARP4 using MODELLER v9.22 algorithm and examined the interaction with Autodock v4.2 in computer environment, we observed that the enzyme is connected with a common motif similar to PARP1 and PARP2. When PARP1 and PARP2 interact with this common motif with NAD, we experimentally observed that these structures interact directly with NAD in order to undergo catalytic reactions by Thermal-Shift assay. The PARP4–NAD complex with the binding energy −26.73 kJ/mol was further used for molecular dynamics analysis. Root mean square deviation (RMSD) for all backbone atoms, electrostatic energy, van der Waals energy of PARP4-NAD complex were studied in the form of molecular dynamics trajectories to throw light on the medically important PARP family of enzymes.