Phosphoribosyltransferase

From Proteopedia

Revision as of 21:02, 13 October 2017

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 Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights 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 inosine monophosphate from hypoxanthine[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]. 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: and [12]. .

3D structures of phosphoribosyltransferase

Updated on 13-October-2017

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. ↑ 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
12. ↑ 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