rhSPR His, CF (20 UG)

Background: SPR

Sepiapterin reductase (SPR) catalyzes the biosynthesis of tetra-hydrobiopterin (BH4), an important cofactor in aromatic amino acid metabolism and key regulator of nitric oxide biosynthesis which relates the BH4 cofactor to many pathophysiological processes (1, 2). SPR has additionally been shown to be efficient at mediating chemical redox cycling of quinones and herbicides through a mechanism distinct from sepiapterin reduction (3). SPR is an NADPH-dependent, cytoplasmic enzyme classified as a member of the short-chain dehydrogenase/reductase (SDR) family based on its structural catalytic domain and NADPH binding motifs (4). SPR forms an active homodimer where each monomer contains a key c-terminal asparagine required for activity (3) in addition to the conserved catalytic triad that serves to stabilize protein structure while maintaining cofactor and substrate proximity in a catalytic site composed of several hydrophobic amino acids (4-6). SPR contains the conserved NADPH binding motif at the N-terminus (4-6). SPR has broad tissue expression (7). Identified human mutations in SPR result in compromised production of biopterin cofactor and are associated with neurological deficits (8, 9) linked to dystonia (8, 10). Knockout in mice likewise results in reduced neurotransmitters and movement disorders (11). Loss of BH4 can also reduce nitric oxide production leading to alterations in cardiac function and inflammation (2). SPR has been pharmacologically targeted to reduce pathologically elevated BH4 for pain management (12, 13) and to regulate T-cell function in pathological diseases and tumor growth (14).