5k51 | pdb_00005k51

Trypanosome brucei Hypoxanthine-guanine phosphoribosyltranferase in complex with a 9-[5-(phosphonoheptyl]hypoxanthine

spinqualitylabelsall models 5k51, resolution 2.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5k51 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6QD Related: 5jsq, 5jv5, 5kam, 5kap Activity: Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 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 Human African Trypanosomiasis (HAT) is a life-threatening infectious disease caused by the protozoan parasite, Trypanosoma brucei (Tbr). Due to the debilitating side effects of the current therapeutics and the emergence of resistance to these drugs, new medications for this disease need to be developed. One potential new drug target is 6-oxopurine phosphoribosyltransferase (PRT), an enzyme central to the purine salvage pathway and whose activity is critical for the production of the nucleotides (GMP and IMP) required for DNA/RNA synthesis within this protozoan parasite. Here, the first crystal structures of this enzyme have been determined, these in complex with GMP and IMP and with three acyclic nucleoside phosphonate (ANP) inhibitors. The Ki values for GMP and IMP are 30.5 muM and 77 muM, respectively. Two of the ANPs have Ki values considerably lower than for the nucleotides, 2.3 muM (with guanine as base) and 15.8 muM (with hypoxanthine as base). The crystal structures show that when two of the ANPs bind, they induce an unusual conformation change to the loop where the reaction product, pyrophosphate, is expected to bind. This and other structural differences between the Tbr and human enzymes suggest selective inhibitors for the Tbr enzyme can be designed. Crystal structures and inhibition of Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase.,Teran D, Hockova D, Cesnek M, Zikova A, Naesens L, Keough DT, Guddat LW Sci Rep. 2016 Oct 27;6:35894. doi: 10.1038/srep35894. PMID:27786284 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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