6mxg

Crystal structure of Trypanosoma brucei hypoxanthine-guanine phosphoribosyltranferase in complex with XMP

spinqualitylabelsall models 6mxg, resolution 2.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6mxg is a 2 chain structure with sequence from Trypanosoma brucei brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.392Å Ligands: MG, SO4, XMP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HPRT_TRYBB 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 (By similarity). Publication Abstract from PubMed The 6-oxopurine phosphoribosyltransferases (PRTs) are drug targets for the treatment of parasitic diseases. This is due to the fact that parasites are auxotrophic for the 6-oxopurine bases relying on salvage enzymes for the synthesis of their 6-oxopurine nucleoside monophosphates. In Trypanosoma brucei, the parasite that is the etiological agent for sleeping sickness, there are three 6-oxopurine PRT isoforms. Two are specific for hypoxanthine and guanine, whilst the third, characterized here, uses all three naturally occurring bases with similar efficiency. Here, we have determined crystal structures for TbrHGXPRT in complex with GMP, XMP and IMP to investigate the structural basis for substrate specificity. The results show that Y201 and E208, not commonly observed within the purine binding pocket of 6-oxopurine PRTs, contribute to the versatility of this enzyme. The structures further show that a nearby water can act as an adaptor to facilitate the binding of XMP and GMP. When GMP binds, a water can accept a proton from the 2-amino group but when XMP binds, the equivalent water can donate its proton to the 2-oxo group. However, when IMP is bound, no water molecule is observed at that location. This article is protected by copyright. All rights reserved. Crystal structures of Trypanosoma brucei hypoxanthine - guanine - xanthine phosphoribosyltransferase in complex with IMP, GMP and XMP.,Teran D, Dolezelova E, Keough DT, Hockova D, Zikova A, Guddat LW FEBS J. 2019 Jul 9. doi: 10.1111/febs.14987. PMID:31287615 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase 3D structures

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