The results of modeling of a novel human histone acetyltransferase Patt1 are presented here. This protein belongs to the GNAT GCN5 family and shows proapoptotic activity in human hepatocellular carcinoma cells. Patt1 is an attractive therapeutic target. The sequence analysis, fold recognition predictions and homology modeling of Patt1 protein structure were performed. N- and C- termini of Patt1 were unstructured. Central part revealed classical GNAT fold-central 7-stranded beta sheet core surrounded by intervening 4 alpha helices. The model was assessed with the methods for protein structure validation PROQ and MetaMQAPII. The all-atom 12 ns molecular dynamics simulation of Patt1 model with TIP3P water model and counterions was conducted. All assessment methods implemented resulted in conviction that the model was of quality that could provide confident structural information to infer sequence-structure-function relationships of Patt1. Phe186 and Cys137 were identified as residues engaged in acetyltransfer reaction and the clues for the identification of reaction mechanism were proposed. The knowledge of detailed molecular architecture of Patt1 is not only the key to understanding its mechanistic functional properties but it also opens the possibility of rational drug and protein design experiments, leading to development of effective therapeutic methods.
