Detecting a novel motif of O6-methyl guanine DNA methyltransferase, a DNA repair enzyme, involved in interaction with proliferating cell nuclear antigen through a computer modeling approach

• Published in: Computational and theoretical chemistry 2021-12, Vol.1206, p.113471, Article 113471
• Main Authors: Gharouni, Marzieh, Mosaddeghi, Hamid, Mehrzad, Jamshid, Es-haghi, Ali, Motavalizadehkakhky, Alireza
• Format: Article
• Language: English
• Subjects: APIM motif; MGMT; Molecular dynamics; PCNA; Protein-Protein interaction
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2021.113471

[Display omitted] •Proteins that interact with PCNA have a PCNA-interacting peptide (PIP box) or an AlkB homologue 2 PCNA-interacting motif (APIM) or both of them in their structures.•The key amino acids of MGMT included R96, W100, A119, G122, N123, P124, K125, also known as APIM motif.•According to our simulation results the most common amino acids of PCNA that interact with APIM motif structures are located in its inter domain connector loop (IDCL) and some others are present in the N –terminal and C –terminal domains.•High binding energy value indicates that the two proteins have a great tendency together. In the path of repairing DNA for the defects caused by alkylating compounds, especially methyl group abnormalities, O6-methyl guanine DNA methyltransferase (MGMT) is an essential enzyme that acts by removing the adducts embedded in guanine and thymine’s nucleotide bases of DNA. Proliferating cell nuclear antigen (PCNA), which is a DNA sliding clamp and one of the members of the cell cycle acts in concert with DNA replication or repair proteins. MGMT interacts with PCNA for its repair function via a motif. Notably, we present an investigation focusing on the MGMT-PCNA interaction through molecular dynamics simulation. The analysis of the simulated MGMT-PCNA complex showed that MGMT could interact with PCNA via the AlkB homolog 2 Interacting Motif (APIM). Likewise, we found that the N-terminal and C–terminal domains as well as the inter domain connector loop (IDCL) of PCNA were involved in interacting with the APIM motif of MGMT.