2xbu

Saccharomyces cerevisiae hypoxanthine-guanine phosphoribosyltransferase in complex with GMP (monoclinic crystal form)

spinqualitylabelsall models 2xbu, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xbu is a 2 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5GP, ACT, MG Related: 2jky, 2jkz Activity: Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase 3D structures

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