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| | ==Saccharomyces cerevisiae hypoxanthine-guanine phosphoribosyltransferase in complex with GMP (monoclinic crystal form)== | | ==Saccharomyces cerevisiae hypoxanthine-guanine phosphoribosyltransferase in complex with GMP (monoclinic crystal form)== |
| - | <StructureSection load='2xbu' size='340' side='right' caption='[[2xbu]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='2xbu' size='340' side='right'caption='[[2xbu]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xbu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XBU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XBU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xbu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XBU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jky|2jky]], [[2jkz|2jkz]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xbu OCA], [https://pdbe.org/2xbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xbu RCSB], [https://www.ebi.ac.uk/pdbsum/2xbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xbu ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xbu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xbu RCSB], [http://www.ebi.ac.uk/pdbsum/2xbu PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HPRT_YEAST HPRT_YEAST]] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.<ref>PMID:371963</ref> <ref>PMID:6170313</ref> <ref>PMID:7035445</ref> <ref>PMID:6392474</ref> <ref>PMID:9335580</ref> <ref>PMID:11035032</ref> <ref>PMID:18245832</ref> | + | [https://www.uniprot.org/uniprot/HPRT_YEAST HPRT_YEAST] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.<ref>PMID:371963</ref> <ref>PMID:6170313</ref> <ref>PMID:7035445</ref> <ref>PMID:6392474</ref> <ref>PMID:9335580</ref> <ref>PMID:11035032</ref> <ref>PMID:18245832</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2xbu" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | + | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hypoxanthine phosphoribosyltransferase]] | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Boissier, F]] | + | [[Category: Boissier F]] |
| - | [[Category: Breton, A]] | + | [[Category: Breton A]] |
| - | [[Category: Daignan-Fornier, B]] | + | [[Category: Daignan-Fornier B]] |
| - | [[Category: Dautant, A]] | + | [[Category: Dautant A]] |
| - | [[Category: Giraud, M F]] | + | [[Category: Giraud MF]] |
| - | [[Category: Moynie, L]] | + | [[Category: Moynie L]] |
| - | [[Category: Flip peptide-plane]]
| + | |
| - | [[Category: Glycosyltransferase]]
| + | |
| - | [[Category: Purine salvage]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
HPRT_YEAST Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine recycling pathway that catalyzes the conversion of 5-phospho-ribosyl-alpha-1-pyrophosphate and guanine or hypoxanthine to guanosine monophosphate (GMP) or inosine monophosphate (IMP), respectively, and pyrophosphate (PPi). We report the first crystal structure of a fungal 6-oxopurine phosphoribosyltransferase, the Saccharomyces cerevisiae HGPRT (Sc-HGPRT) in complex with GMP. The crystal structures of full length protein with (WT1) or without (WT2) sulfate that mimics the phosphate group in the PPi binding site were solved by molecular replacement using the structure of a truncated version (Delta7) solved beforehand by multiwavelength anomalous diffusion. Sc-HGPRT is a dimer and adopts the overall structure of class I phosphoribosyltransferases (PRTs) with a smaller hood domain and a short two-stranded parallel beta-sheet linking the N- to the C-terminal end. The catalytic loops in WT1 and WT2 are in an open form while in Delta7, due to an inter-subunit disulfide bridge, the catalytic loop is in either an open or closed form. The closure is concomitant with a peptide plane flipping in the PPi binding loop. Moreover, owing the flexibility of a GGGG motif conserved in fungi, all the peptide bonds of the phosphate binding loop are in trans conformation whereas in nonfungal 6-oxopurine PRTs, one cis-peptide bond is required for phosphate binding. Mutations affecting the enzyme activity or the previously characterized feedback inhibition by GMP are located at the nucleotide binding site and the dimer interface.
Functional significance of four successive glycine residues in the pyrophosphate binding loop of fungal 6-oxopurine phosphoribosyltransferases.,Moynie L, Giraud MF, Breton A, Boissier F, Daignan-Fornier B, Dautant A Protein Sci. 2012 Aug;21(8):1185-96. doi: 10.1002/pro.2098. Epub 2012 Jun 11. PMID:22610485[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schmidt R, Wiegand H, Reichert U. Purification and characterization of the hypoxanthine-guanine phosphoribosyltransferase from Saccharomyces cerevisiae. Eur J Biochem. 1979 Jan 15;93(2):355-61. PMID:371963
- ↑ Nussbaum RL, Caskey CT. Purification and characterization of hypoxanthine-guanine phosphoribosyltransferase from Saccharomyces cerevisiae. Biochemistry. 1981 Aug 4;20(16):4584-90. PMID:6170313
- ↑ Ali LZ, Sloan DL. Studies of the kinetic mechanism of hypoxanthine-guanine phosphoribosyltransferase from yeast. J Biol Chem. 1982 Feb 10;257(3):1149-55. PMID:7035445
- ↑ Woods RA, Roberts DG, Stein DS, Filpula D. Adenine phosphoribosyltransferase mutants in Saccharomyces cerevisiae. J Gen Microbiol. 1984 Oct;130(10):2629-37. PMID:6392474
- ↑ Guetsova ML, Lecoq K, Daignan-Fornier B. The isolation and characterization of Saccharomyces cerevisiae mutants that constitutively express purine biosynthetic genes. Genetics. 1997 Oct;147(2):383-97. PMID:9335580
- ↑ Escobar-Henriques M, Daignan-Fornier B. Transcriptional regulation of the yeast gmp synthesis pathway by its end products. J Biol Chem. 2001 Jan 12;276(2):1523-30. PMID:11035032 doi:http://dx.doi.org/10.1074/jbc.M007926200
- ↑ Breton A, Pinson B, Coulpier F, Giraud MF, Dautant A, Daignan-Fornier B. Lethal accumulation of guanylic nucleotides in Saccharomyces cerevisiae HPT1-deregulated mutants. Genetics. 2008 Feb;178(2):815-24. Epub 2008 Feb 3. PMID:18245832 doi:10.1534/genetics.107.083295
- ↑ Moynie L, Giraud MF, Breton A, Boissier F, Daignan-Fornier B, Dautant A. Functional significance of four successive glycine residues in the pyrophosphate binding loop of fungal 6-oxopurine phosphoribosyltransferases. Protein Sci. 2012 Aug;21(8):1185-96. doi: 10.1002/pro.2098. Epub 2012 Jun 11. PMID:22610485 doi:http://dx.doi.org/10.1002/pro.2098
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