S. cerevisiae orotate phosphoribosyl transferase bound to its substrates. From PDB file 2PS1.
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Orotate phosphoribosyltransferase (OPRTase) or orotic acid phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate. In yeast and bacteria, orotate phosphoribosyltransferase is an independent enzyme with a unique gene coding for the protein, whereas in mammals and other multicellular organisms, the catalytic function is carried out by a domain of the bifunctional enzyme UMP synthase.
As OPRTase is part of a bifunctional complex UMP synthase in humans, the function and stability of this enzyme is not necessarily directly associated with disorders in the human body. It is however reasonable to believe that a dysfunction in one of the enzymes will cause a dysfunction of the whole enzyme. Defects in UMP synthase is associated with hypochromic anemia.
Protein structure and function
The crystal structure of OPRTase has been solved several times by various scientific groups. The overall structure is a dimer of two subunits, each consisting of seven α-helices and ten β-strands. The active site can be closed by a flexible loop, that prevents solvent from entering during reaction.
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- Henriksen A, Aghajari N, Jensen KF, Gajhede M (1996). "A Flexible Loop at the Dimer Interface Is a Part of the Active Site of the Adjacent Monomer of Escherichia Coli Orotate Phosphoribosyltransferase". Biochemistry. 35 (12): 3803–3809. doi:10.1021/bi952226y. PMID 8620002.
- Scapin G, Grubmeyer C, Sacchettini JC (1994). "Crystal Structure of Orotate Phosphoribosyltransferase". Biochemistry. 33 (6): 1287–1294. doi:10.1021/bi00172a001.