1STO
CRYSTAL STRUCTURE OF OROTATE PHOSPHORIBOSYLTRANSFERASE
Summary for 1STO
| Entry DOI | 10.2210/pdb1sto/pdb |
| Descriptor | OROTATE PHOSPHORIBOSYLTRANSFERASE, OROTIDINE-5'-MONOPHOSPHATE (3 entities in total) |
| Functional Keywords | phosphoribosyltransferase |
| Biological source | Salmonella typhimurium |
| Total number of polymer chains | 1 |
| Total formula weight | 23902.13 |
| Authors | Scapin, G.,Grubmeyer, C.,Sacchettini, J.C. (deposition date: 1993-12-20, release date: 1994-05-31, Last modification date: 2024-09-25) |
| Primary citation | Scapin, G.,Grubmeyer, C.,Sacchettini, J.C. Crystal structure of orotate phosphoribosyltransferase. Biochemistry, 33:1287-1294, 1994 Cited by PubMed Abstract: Phosphoribosyltransferases (PRTases) are enzymes involved in the synthesis of purine, pyrimidine, and pyridine nucleotides. They utilize alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and a nitrogenous base to form a beta-N-riboside monophosphate and pyrophosphate (PPi), and their functional significance in nucleotide homeostasis is evidenced by the devastating effects of inherited diseases associated with the decreased activity and/or stability of these enzymes. The 2.6-A structure of the Salmonella typhimurium orotate phosphoribosyltransferase (OPRTase) complexed with its product orotidine monophosphate (OMP) provides the first detailed image of a member of this group of enzymes. The OPRTase three-dimensional structure was solved using multiple isomorphous replacement methods and reveals two major features: a core five-stranded alpha/beta twisted sheet and an N-terminal region that partially covers the C-terminal portion of the core. PRTases show a very high degree of base specificity. In OPRTase, this is determined by steric constraints and the position of hydrogen bond donors/acceptors of a solvent-inaccessible crevice where the orotate ring of bound OMP resides. Crystalline OPRTase is a dimer, with catalytically important residues from each subunit available to the neighboring subunit, suggesting that oligomerization is necessary for its activity. On the basis of the presence of a common PRPP binding motif among PRTases and the similar chemistry these enzymes perform, we propose that the alpha/beta core found in OPRTase will represent a common feature for PRTases. This generality is demonstrated by construction of a model of the human hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) from secondary structure predictions for HGPRTase and the three-dimensional structure of OPRTase. PubMed: 8312245DOI: 10.1021/bi00172a001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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