Lead discovery and in silico 3D structure modeling of tumorigenic FAM72A (p17)

Abstract

FAM72A (p17) is a novel neuronal protein that has been linked to tumorigenic effects in non-neuronal tissue. Using state of the art in silico physicochemical analyses (e.g., I-TASSER, RaptorX, and Modeller), we determined the three-dimensional (3D) protein structure of FAM72A and further identified potential ligand-protein interactions. Our data indicate a Zn(2+)/Fe(3+)-containing 3D protein structure, based on a 3GA3_A model template, which potentially interacts with the organic molecule RSM ((2s)-2-(acetylamino)-N-methyl-4-[(R)-methylsulfinyl] butanamide). The discovery of RSM may serve as potential lead for further anti-FAM72A drug screening tests in the pharmaceutical industry because interference with FAM72A's activities via RSM-related molecules might be a novel option to influence the tumor suppressor protein p53 signaling pathways for the treatment of various types of cancers.

All-or-(N)One – an epistemological characterization of the human tumorigenic neuronal paralogous FAM72 gene loci

“…4). Because FAM72 seems to characterize pathologically proliferating cells outside of the nervous system but is otherwise absent, it is an interesting therapeutic drug target candidate in cancer [68]. In this regard, it is notable that a GWA in East Asians identified a breast cancer susceptibility locus at 1q32.1 (FAM72A) within intron 2 of ZC3H11A and the 5′ UTR of the ZBED6 (~2300 kbp downstream of FAM72A) [69].…”

3D Structure, Dimerization Modeling, and Lead Discovery by Ligand‐protein Interaction Analysis of p60 Transcription Regulator Protein (p60TRP)

“…The pre‐analyzed suggested templates from the NCBI‐PDB database, Phyre2, ModBase, and Swiss Model were subjected to comparative modeling using Modeller v.9.13 software as described17,20 and applied previously 21–26. The best suggested 3D p60TRP protein structures based on templates from RaptorX were also applied to comparative modeling analysis using Modeller v.9.13 software.…”

Proteomic Atomics Reveals a Distinctive Uracil‐5‐Methyltransferase

“…The 3D structural relationships among the various modeled 3D Pf3D7 U5MTase protein structures were tested, and the stereochemical qualities of obtained U5MTase models were ultimately evaluated with various programs (e. g., PROCHECK, PSVS, and ProSA) to prove the structural quality of the in silico 3D Pf3D7 U5MTase protein structures (including Ramachandran plot, main chain and side chain parameters, and stereochemical quality-check of the by VERIFY3D and ERRAT (http:// nihserver.mbi.ucla.edu/SAVES/)) and to select the best model for further detection of potential ligand binding sites. For further details refer to Pramanik et al, 2015Pramanik et al, , 2016 Finally, the full-length ab initio 3D Pf3D7 U5MTase protein structure model (from Phyre2, with refinement by ModRefiner [10] ) was selected. For further details refer to Pramanik et al, 2015Pramanik et al, , 2016 Further application of COACH, TM-SITE, S-SITE, COFAC-TOR, and ConCavity approaches provided potential ligandbinding sites of the selected 3D U5MTase protein structure model (full length ab initio model with refinement by ModRefiner [10] ) with various molecules based on a BioLiP.…”

“…For further details refer to Pramanik et al, 2015Pramanik et al, , 2016 Finally, the full-length ab initio 3D Pf3D7 U5MTase protein structure model (from Phyre2, with refinement by ModRefiner [10] ) was selected. For further details refer to Pramanik et al, 2015Pramanik et al, , 2016 Further application of COACH, TM-SITE, S-SITE, COFAC-TOR, and ConCavity approaches provided potential ligandbinding sites of the selected 3D U5MTase protein structure model (full length ab initio model with refinement by ModRefiner [10] ) with various molecules based on a BioLiP. [11] The MTiOpenScreen [12] database was applied for chemical library virtual screening.…”