Protein-protein interfaces as druggable targets: A common motif of the pyridoxal-5’-phosphate-dependent enzymes to receive the coenzyme from its producers

Abstract

The enzymes using pyridoxal-5’-phosphate (PLP) as the coenzyme encompass more than 300 31 distinct catalytic functions, belonging to five of the seven existing EC classes [1]. Many of these 32 reactions, particularly those involving amino acid metabolism, are critical for not only metabolic 33 switches underlying malformations, but also the elimination of malignant cells. For instance, PLP- 34 dependent transaminases drive T cells activation and differentiation, required for anticancer 35 responses [2]. Down-regulation of the PLP-dependent tyrosine aminotransferase (TAT) encoded by 36 TAT gene, supports pathogenicity of hepatocellular carcinoma [3], with the low expression of the 37 tyrosine catabolic enzymes predicting poor outcome [4].