Adenine phosphoribosyltransferase

1ZN9, 1ORE, 1ZN7, 1ZN8, 4X44, 4X4535311821ENSG00000198931ENSMUSG00000006589P07741P08030NM_001030018NM_000485NM_009698NP_000476NP_001025189NP_033828Adenine phosphoribosyltransferase (APRTase) is an enzyme encoded by the APRT gene, found in humans on chromosome 16. It is part of the Type I PRTase family and is involved in the nucleotide salvage pathway, which provides an alternative to nucleotide biosynthesis de novo in humans and most other animals. In parasitic protozoa such as giardia, APRTase provides the sole mechanism by which adenine can be produced. APRTase deficiency contributes to the formation of kidney stones (urolithiasis) and to potential kidney failure.1ore: Human Adenine Phosphoribosyltransferase1zn7: Human Adenine Phosphoribosyltransferase Complexed with PRPP, ADE and R5P1zn8: Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution1zn9: Human Adenine Phosphoribosyltransferase in Apo and AMP Complexed Forms Adenine phosphoribosyltransferase (APRTase) is an enzyme encoded by the APRT gene, found in humans on chromosome 16. It is part of the Type I PRTase family and is involved in the nucleotide salvage pathway, which provides an alternative to nucleotide biosynthesis de novo in humans and most other animals. In parasitic protozoa such as giardia, APRTase provides the sole mechanism by which adenine can be produced. APRTase deficiency contributes to the formation of kidney stones (urolithiasis) and to potential kidney failure. APRTase catalyzes the following reaction in the purine nucleotide salvage pathway: Adenine + Phosphoribosyl Pyrophosphate (PRPP) → Adenylate (AMP) + Pyrophosphate (PPi) In organisms that can synthesize purines de novo, the nucleotide salvage pathway provides an alternative that is energetically more efficient. It can salvage adenine from the polyamine biosynthetic pathway or from dietary sources of purines. Although APRTase is functionally redundant in these organisms, it becomes more important during periods of rapid growth, such as embryogenesis and tumor growth. It is constitutively expressed in all mammalian tissue. In protozoan parasites, the nucleotide salvage pathway provides the sole means for nucleotide synthesis. Since the consequences of APRTase deficiency in humans is comparatively mild and treatable, it may be possible to treat certain parasitic infections by targeting APRTase function. In plants, as in other organisms, ARPTase functions primarily for the synthesis of adenylate. It has the unique ability to metabolize cytokinins—a plant hormone that can exist as a base, nucleotide, or nucleoside—into adenylate nucleotides. APRT is functionally related to hypoxanthine-guanine phosphoribosyltransferase (HPRT). APRTase is a homodimer, with 179 amino acid residues per monomer. Each monomer contains the following regions: The core is highly conserved across many PRTases. The hood, which contains the adenine binding site, has more variability within the family of enzymes. A 13-residue motif comprises the PRPP binding region and involves two adjacent acidic residues and at least one surrounding hydrophobic residue.