Phosphoribosyltransferase

From Proteopedia

Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights 5 3D structures of phosphoribosyltransferase Function Phosphoribosyltransferase (PRT) are transferases which belong to several classes: 1. Hypoxanthine-guanine PRT (HPRT). HPRT is part of the purine biosynthesis and catalyzes the formation of GMP from guanine, xanthosine monophosphate from xanthosine and of IMP from hypoxanthine and phosphoribosyl pyrophosphate (PRPP)[1]. 2. Orotate PRT (OPRT). OPRT is part of the pyrimidine biosynthesis and catalyzes the formation of orotidine 5’-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate (PRPP)[2]. 3. Quinolinic acid PRT (QAPRT ). QAPRT is a degrading enzyme found in the brain[3]. 4. Uracil PRT (UPRT). UPRT catalyzes the formation of UMP from uracil and PRPP. Adenine PRT (APRT). APRT catalyzes the formation of AMP from adenine and PRPP[4]. 5. Nicotinate nucleotide dimethylbenzimidazole PRT (NN:DBI PRT). NN:DBI PRT is part of riboflavin, porphyrin and chlorophyll biosynthesis[5]. 6. Anthranilate PRT (ANPRT). ANPRT participates in phenylalanine, tyrosine and tryptophan biosynthesis and catalyzes the formation of anthraniline from phosphoribosyl anthranilate[6]. 7. ATP PRT participates in histidine biosynthesis and catalyzes the formation of ATP from phosphoribosyl ATP and diphosphate[7]. See ATP Phosphoribosyl Transferase. 8. Nicotinate PRT (NIPRT). NIPRT catalyzes the formation of nicotinate from nicotinate ribonucleotide and diphosphate[8]. 9. Nicotinamide PRT (NMPRT). NMPRT catalyzes the formation of nicotinamide from nicotinamide ribonucleotide (NMN) and diphosphate[9]. Disease Mutations in HPRT are involved in Lesch-Nyhan syndrome and hereditary gout[10]. Relevance NMPRT inhibition is a target in controlling inflammation disorders[11]. Structural highlights The structure of the yeast OPRT contains the two reaction products: orotate and PRPP[2]. Mg coordination site. Water molecules are shown as red spheres. Whole binding site. 3D structures of phosphoribosyltransferase Phosphoribosyltransferase 3D structures

spinqualitylabelsall models Yeast orotate phosphoribosyltransferase dimer complex with orotate and PRPP (PDB entry 2ps1) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

References

1. ↑ Sculley DG, Dawson PA, Emmerson BT, Gordon RB. A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Hum Genet. 1992 Nov;90(3):195-207. PMID:1487231
2. ↑ ^{2.0 2.1} Gonzalez-Segura L, Witte JF, McClard RW, Hurley TD. Ternary complex formation and induced asymmetry in orotate phosphoribosyltransferase. Biochemistry. 2007 Dec 11;46(49):14075-86. Epub 2007 Nov 20. PMID:18020427 doi:10.1021/bi701023z
3. ↑ Foster AC, Whetsell WO Jr, Bird ED, Schwarcz R. Quinolinic acid phosphoribosyltransferase in human and rat brain: activity in Huntington's disease and in quinolinate-lesioned rat striatum. Brain Res. 1985 Jun 17;336(2):207-14. PMID:3159462
4. ↑ Carter D, Donald RG, Roos D, Ullman B. Expression, purification, and characterization of uracil phosphoribosyltransferase from Toxoplasma gondii. Mol Biochem Parasitol. 1997 Aug;87(2):137-44. PMID:9247925
5. ↑ . PMID:121011881
6. ↑ Castell A, Short FL, Evans GL, Cookson TV, Bulloch EM, Joseph DD, Lee CE, Parker EJ, Baker EN, Lott JS. Substrate capture mechanism of Mycobacterium tuberculosis anthranilate phosphoribosyltransferase provides a mode for inhibition. Biochemistry. 2013 Jan 30. PMID:23363292 doi:http://dx.doi.org/10.1021/bi301387m
7. ↑ Pedreno S, Pisco JP, Larrouy-Maumus G, Kelly G, de Carvalho LP. Mechanism of feedback allosteric inhibition of ATP phosphoribosyltransferase. Biochemistry. 2012 Oct 9;51(40):8027-38. doi: 10.1021/bi300808b. Epub 2012 Sep, 27. PMID:22989207 doi:http://dx.doi.org/10.1021/bi300808b
8. ↑ Galassi L, Di Stefano M, Brunetti L, Orsomando G, Amici A, Ruggieri S, Magni G. Characterization of human nicotinate phosphoribosyltransferase: Kinetic studies, structure prediction and functional analysis by site-directed mutagenesis. Biochimie. 2012 Feb;94(2):300-9. doi: 10.1016/j.biochi.2011.06.033. Epub 2011 Jul, 3. PMID:21742010 doi:http://dx.doi.org/10.1016/j.biochi.2011.06.033
9. ↑ Imai S. Nicotinamide phosphoribosyltransferase (Nampt): a link between NAD biology, metabolism, and diseases. Curr Pharm Des. 2009;15(1):20-8. PMID:19149599
10. ↑ Tohyama J, Nanba E, Ohno K. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: identification of point mutations in Japanese patients with Lesch-Nyhan syndrome and hereditary gout and their permanent expression in an HPRT-deficient mouse cell line. Hum Genet. 1994 Feb;93(2):175-81. PMID:8112742
11. ↑ Montecucco F, Cea M, Cagnetta A, Damonte P, Nahimana A, Ballestrero A, Del Rio A, Bruzzone S, Nencioni A. Nicotinamide phosphoribosyltransferase as a target in inflammation- related disorders. Curr Top Med Chem. 2013;13(23):2930-8. PMID:24171767