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evolution
adenylate kinase (EC 2.7.4.3, AMPK) belongs to nucleoside-5'-monophosphate kinase (NMPK) family. ZgHGPRT/AMPK belongs to class I PRTs, which display a conserved 13-residue fingerprint region (PRPP binding-motif) in their amino acid sequence
evolution
four substitutions are identified in the region of the active site between SmHGPRT and human HGPRT: Ile149Met, Pro176Arg, Val189Ile, and Arg192Lys
evolution
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adenylate kinase (EC 2.7.4.3, AMPK) belongs to nucleoside-5'-monophosphate kinase (NMPK) family. ZgHGPRT/AMPK belongs to class I PRTs, which display a conserved 13-residue fingerprint region (PRPP binding-motif) in their amino acid sequence
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evolution
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adenylate kinase (EC 2.7.4.3, AMPK) belongs to nucleoside-5'-monophosphate kinase (NMPK) family. ZgHGPRT/AMPK belongs to class I PRTs, which display a conserved 13-residue fingerprint region (PRPP binding-motif) in their amino acid sequence
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evolution
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adenylate kinase (EC 2.7.4.3, AMPK) belongs to nucleoside-5'-monophosphate kinase (NMPK) family. ZgHGPRT/AMPK belongs to class I PRTs, which display a conserved 13-residue fingerprint region (PRPP binding-motif) in their amino acid sequence
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evolution
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adenylate kinase (EC 2.7.4.3, AMPK) belongs to nucleoside-5'-monophosphate kinase (NMPK) family. ZgHGPRT/AMPK belongs to class I PRTs, which display a conserved 13-residue fingerprint region (PRPP binding-motif) in their amino acid sequence
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evolution
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adenylate kinase (EC 2.7.4.3, AMPK) belongs to nucleoside-5'-monophosphate kinase (NMPK) family. ZgHGPRT/AMPK belongs to class I PRTs, which display a conserved 13-residue fingerprint region (PRPP binding-motif) in their amino acid sequence
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malfunction
a deficiency in HPRT activity leads to overproduction of uric acid, hyperuricemia, with gouty arthritis, nephrolithiasis, and mild neurologic symptoms. According to the degree of enzymatic deficiency, a large spectrum of neurologic features can also be observed, ranging from mild or no neurologic involvement to complete Lesch-Nyhan disease
malfunction
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complete deficiency of hypoxanthine-guanine phosphoribosyltransferase causes the Lesch-Nyhan disease, a genetic disorder associated with motor and psychiatric disturbance and self-injurious behaviour, the role of serotonin receptor 2C, HTR2C, might be involved, overview
malfunction
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HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype, and is involved in Lesch-Nyhan disease pathogenesis
malfunction
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mutations in the gene encoding the purine biosynthetic enzyme HPRT cause the resulting intractable and largely untreatable neurological impairment of Lesch-Nyhan disease. The disorder is associated with a defect in basal ganglia DA pathways, phenotype mechanisms analysis in human embryonic carcinoma neurogenesis model, overview
malfunction
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enzyme knockdown causes a marked switch from neuronal to glial gene expression and dysregulates expression of Sox2 and its regulator, genes vital for stem cell pluripotency and for the neuronal/glial cell fate decision. In addition, enzyme deficiency dysregulates many cellular functions controlling cell cycle and proliferation mechanisms, RNA metabolism, DNA replication and repair, replication stress, lysosome function, membrane trafficking, signaling pathway for platelet activation multiple neurotransmission systems and sphingolipid, sulfur and glycan metabolism
malfunction
deletion of the HGPRT gene (DELTAhgprt) in the model organism Mycobacterium smegmatis confirms that this enzyme is not essential for Mycobacterium smegmatis' growth
malfunction
the Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The role of the amyloid precursor protein (APP) gene in neuropathology is associated with HGprt-deficiency in LND. Classical features of LND include hyperuricemia and its sequelae (gout, nephrolithiasis, and tophi), motor disability (dystonia, chorea, and spasticity), intellectual impairment, and self-injurious behaviors such as self-biting, self-hitting, eye poking, and others. Self-injurious behavior is universal in LND. It usually emerges before 4 years of age, but may be delayed until the second decade of life. Etiology involves a mutation of the housekeeping hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene that is located on the long arm of the X chromosome (Xq26.1)
malfunction
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deletion of the HGPRT gene (DELTAhgprt) in the model organism Mycobacterium smegmatis confirms that this enzyme is not essential for Mycobacterium smegmatis' growth
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malfunction
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deletion of the HGPRT gene (DELTAhgprt) in the model organism Mycobacterium smegmatis confirms that this enzyme is not essential for Mycobacterium smegmatis' growth
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metabolism
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comparison of growth characteristics including intracellular protein levels, RNA content, and nucleotide pool sizes between the extreme halophile Halobacterium halobium and the moderate halophile Haloferax volcanii. The differences in the metabolism of purine bases and nucleosides and the sensitivity to purine analogs between the two halobacteria are reflected in differences in purine enzyme levels
metabolism
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comparison of growth characteristics including intracellular protein levels, RNA content, and nucleotide pool sizes between the extreme halophile Halobacterium halobium and the moderate halophile Haloferax volcanii. The differences in the metabolism of purine bases and nucleosides and the sensitivity to purine analogs between the two halobacteria are reflected in differences in purine enzyme levels
metabolism
analysis of the molecular basis to understand the 6-oxopurine salvage in Trypansoma brucei
metabolism
in Escherichia coli, the purine salvage pathway has two 6-oxopurine phosphoribosyltransferases (PRTs), xanthine-guanine PRT (EcXGPRT, EC 2.4.2.22) and hypoxanthine PRT (EcHPRT, EC 2.4.2.8). Escherichia coli can utilize both purine salvage and de novo pathways for the production of the nucleoside monophosphates required for incorporation into DNA and RNA. Escherichia coli is highly unusual in that it is one of only a few organisms that possess two distinct salvage enzymes for 6-oxopurine nucleoside monophosphate production
metabolism
Schistosoma mansoni parasite lacks the de novo purine biosynthetic pathway and depends entirely on the purine salvage pathway for the supply of purines. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine salvage pathway
metabolism
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the enzyme is important in the purine metabolism pathways. Analysis and comparison of plasma and red blood cell hypoxanthine and inosine monophosphate concentrations and enzyme activities from bottlenose dolphins (Tursiops truncatus) and humans, overview. Hypoxanthine and inosine monophosphate concentrations are higher in plasma from dolphins than humans. Plasma hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity in dolphins suggests an elevated purine recycling rate, and a mechanism for avoiding accumulation of non-recyclable purines (xanthine and uric acid). Red blood cell concentrations of hypoxanthine, adenosine diphosphate, ATP, and guanosine triphosphate are lower in dolphins than in humans. Adenosine monophosphate and nicotinamide adenine dinucleotide concentrations are higher in dolphins. HGPRT activity in red blood cells is higher in humans than in dolphins. The lower concentrations of purine catabolism and recycling by-products in plasma from dolphins ca be beneficial in providing substrates for recovery of ATP-depletion during diving or vigorous swimming. The results suggest that purine salvage in dolphins could be a mechanism for delivering nucleotide precursors to tissues with high ATP and guanosine triphosphate requirements
metabolism
the enzyme is important in the purine metabolism pathways. Analysis and comparison of plasma and red blood cell hypoxanthine and inosine monophosphate concentrations and enzyme activities from bottlenose dolphins (Tursiops truncatus) and humans, overview. Hypoxanthine and inosine monophosphate concentrations are higher in plasma from dolphins than humans. Red blood cell concentrations of hypoxanthine, adenosine diphosphate, ATP, and guanosine triphosphate are lower in dolphins than in humans. Adenosine monophosphate and nicotinamide adenine dinucleotide concentrations are higher in dolphins. HGPRT activity in red blood cells is higher in humans than in dolphins
metabolism
the metabolism of the protozoan parasite Trypanosoma cruzi depends on the salvage of exogenous purines for nucleotide synthesis. In this context, TcHPRT plays a key role in the survival of trypanosomes in their hosts
physiological function
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HPRT is a housekeeping enzyme responsible for recycling purines, it regulates early developmental programming of dopamine neurons
physiological function
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the enzyme enables the reutilization of purine base adenine converting it to mononucleotide AMP, substrate for the synthesis of high-energy nucleotides
physiological function
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the enzyme enables the reutilization of purine base adenine converting it to mononucleotide AMP, substrate for the synthesis of high-energy nucleotides
physiological function
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the enzyme is involved in the specification and development of neurons, including dopaminergic neurons, as well as in the regulation of dopaminergic transcription factors, overview
physiological function
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the purine salvage enzyme HGXPRT is essential for purine nucleotide and hence nucleic acid synthesis in the malaria parasite
physiological function
production of enzyme-deficient human Coxsackievirus-induced pluripotent stem cells and human HUES11 embryonic stem cells using shRNA. Both cells show >99% enzyme knock-down and demonstrate markedly decreased expression of the purinergic P2Y1 receptor mRNA. In Coxsackievirus-induced cells, P2Y1 mRNA and protein down-regulation by hypoxanthine phosphoribosyltransferase knockdown is refractory to activation by the P2Y1 receptor agonist ATP and shows aberrant purinergic signaling, as reflected by marked deficiency of the transcription factor pCREB and constitutive activation of the MAP kinases phospho-ERK1/2. Moreover, hypoxanthine phosphoribosyltransferase-knockdown Coxsackievirus-induced cells also demonstrate marked reduction of phosphorylated beta-catenin
physiological function
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treatment of cells with guanosine and GMP results in statistically significant decreases in cell growth after 48 h and 72 h in the melanoma cell line C32 and in the U-87 glioma cell line. Presence of hypoxanthine blocks the antiproliferative effects. Hypoxanthine phosphoribosyltransferase-negative cell line C32-TG cells completely has lost the inhibitory response to guanine treatment. Hypoxanthine phosphoribosyltransferase silencing by siRNA is able to partially block the guanine-induced antiproliferative effects in U-87 glioma cell lines
physiological function
6-oxopurine phosphoribosyltransferase (PRT) is an enzyme central to the purine salvage pathway, whose activity is critical for the production of nucleotides GMP and IMP that are required for DNA/RNA synthesis within the protozoan parasite
physiological function
having functional salvage pathway enzymes is important in the survival and functionality of mammalian cells. Salvage enzymes, such as HPRT, are known as common housekeeping genes, and are integral in several daily cellular functions regulating cell proliferation and cell cycle progression
physiological function
hypoxanthine is a key precursor salvaged for purine nucleotide synthesis in Plasmodium falciparum, and the most critical enzyme is hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) which catalyzes the freely reversible Mg2+-dependent conversion of 6-oxopurine bases to their respective nucleotides and diphosphate. The phosphoribosyl group is derived from 5-phospho-alpha-D-ribosyl 1-diphosphate (PRPP). The enzyme from malaria parasites (PfHGXPRT) is essential as hypoxanthine is the major precursor in purine metabolism
physiological function
hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the formation of guanosine-5'-monophosphate from guanine and inosine-5'-monophosphate from hypoxanthine. It is the key enzyme in the purine salvage pathway, catalyzes the synthesis of inosine- or guanosine-5'-monophosphate via replacement of the 1-diphosphate group in phosphoribosyl diphosphate with a corresponding free nucleobase. Deletion of the HGPRT gene (DELTAhgprt) in the model organism Mycobacterium smegmatis confirms that this enzyme is not essential for Mycobacterium smegmatis' growth
physiological function
hypoxanthine-guanine-(xanthine) phosphoribosyltransferases, HG(X)PRTs, catalyze the formation of the 6-oxopurine nucleoside monophosphates from a nucleobase and from 5'-phospho-alpha-D-ribosyl-1-diphosphate
physiological function
hypoxanthine-guanine-(xanthine) phosphoribosyltransferases, HG(X)PRTs, catalyze the formation of the 6-oxopurine nucleoside monophosphates from a nucleobase and from 5'-phospho-alpha-D-ribosyl-1-pyrophosphate
physiological function
hypoxanthine-guanine-xanthine phosphoribosyltransference (HGXPRT) is a key enzyme in the purine salvage pathway of the malarial parasite, Plasmodium falciparum (Pf). It catalyses the conversion of hypoxanthine, guanine, and xanthine to their corresponding mononucleotides; IMP, GMP, and XMP, respectively
physiological function
the activity of hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase, HG[X]PRT is essential for the growth of Plasmodium parasites
physiological function
the hypoxanthine phosphoribosyl transferase (TcHPRT) is a critical enzyme in Trypanosoma cruzi for the survival of the parasite. TcHPRT catalyzes the transfer of a mono phosphorylated ribose from phosphoribosyl diphosphate (PRPP) to the purine ring
physiological function
the Zobellia galactanivorans enzyme contains both HGPRT (N-terminal part) and AMPK (C-terminal part) domains. The N-terminal HGPRT module is involved in the purine salvage and converts hypoxanthine to inosine-5'-monophosphate (IMP) and guanine to guanosine-5'-monophosphate (GMP)
physiological function
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the Zobellia galactanivorans enzyme contains both HGPRT (N-terminal part) and AMPK (C-terminal part) domains. The N-terminal HGPRT module is involved in the purine salvage and converts hypoxanthine to inosine-5'-monophosphate (IMP) and guanine to guanosine-5'-monophosphate (GMP)
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physiological function
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the Zobellia galactanivorans enzyme contains both HGPRT (N-terminal part) and AMPK (C-terminal part) domains. The N-terminal HGPRT module is involved in the purine salvage and converts hypoxanthine to inosine-5'-monophosphate (IMP) and guanine to guanosine-5'-monophosphate (GMP)
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physiological function
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hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the formation of guanosine-5'-monophosphate from guanine and inosine-5'-monophosphate from hypoxanthine. It is the key enzyme in the purine salvage pathway, catalyzes the synthesis of inosine- or guanosine-5'-monophosphate via replacement of the 1-diphosphate group in phosphoribosyl diphosphate with a corresponding free nucleobase. Deletion of the HGPRT gene (DELTAhgprt) in the model organism Mycobacterium smegmatis confirms that this enzyme is not essential for Mycobacterium smegmatis' growth
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physiological function
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the Zobellia galactanivorans enzyme contains both HGPRT (N-terminal part) and AMPK (C-terminal part) domains. The N-terminal HGPRT module is involved in the purine salvage and converts hypoxanthine to inosine-5'-monophosphate (IMP) and guanine to guanosine-5'-monophosphate (GMP)
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physiological function
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hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the formation of guanosine-5'-monophosphate from guanine and inosine-5'-monophosphate from hypoxanthine. It is the key enzyme in the purine salvage pathway, catalyzes the synthesis of inosine- or guanosine-5'-monophosphate via replacement of the 1-diphosphate group in phosphoribosyl diphosphate with a corresponding free nucleobase. Deletion of the HGPRT gene (DELTAhgprt) in the model organism Mycobacterium smegmatis confirms that this enzyme is not essential for Mycobacterium smegmatis' growth
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physiological function
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the Zobellia galactanivorans enzyme contains both HGPRT (N-terminal part) and AMPK (C-terminal part) domains. The N-terminal HGPRT module is involved in the purine salvage and converts hypoxanthine to inosine-5'-monophosphate (IMP) and guanine to guanosine-5'-monophosphate (GMP)
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physiological function
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the Zobellia galactanivorans enzyme contains both HGPRT (N-terminal part) and AMPK (C-terminal part) domains. The N-terminal HGPRT module is involved in the purine salvage and converts hypoxanthine to inosine-5'-monophosphate (IMP) and guanine to guanosine-5'-monophosphate (GMP)
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additional information
crystal structures of the enzyme in complex with GMP and IMP and with three acyclic nucleoside phosphonate (ANP) inhibitors are determined. Structure comparisons, overview. One of the most important interactions between a 6-oxopurine PRT and the nucleoside monophosphate is the hydrogen bond between the 6-oxo group and a highly conserved lysine side-chain, K145 in TbrHGPRT. This bond is critical in discriminating the 6-oxopurine from a 6-aminopurine, such as adenine
additional information
crystals of enzyme-diphosphate-GMP complex are used for structure determination, detailed overview
additional information
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crystals of enzyme-diphosphate-GMP complex are used for structure determination, detailed overview
additional information
determination of primary (1-14C and 9-15N) and secondary (1-3H and 7-15N) intrinsic kinetic isotope effect (KIE) values for PfHGXPRT, mass spectrometry. Intrinsic isotope effects contain information for understanding enzymatic transition state properties. The transition state of PfHGXPRT is explored by matching KIE values predicted from quantum mechanical calculations to the intrinsic values determined experimentally. This approach provides information about PfHGXPRT transition state bond lengths, geometry, and atomic charge distribution. The transition state structure of PfHGXPRT is determined in the physiological direction of addition of ribose 5-phosphate to hypoxanthine by overcoming the chemical instability of PRPP. The transition state for PfHGXPRT forms nucleotides through a well-developed and near-symmetrical DN*AN, SN1-like transition state. Structure comparisons to the human enzyme, overview
additional information
identification of a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK). ZgHGPRT/AMPK single domain, dual domain 3D structure homology modeling, HGPRT from Leptospira interrogans (PDB ID 4QRI) and AMPK structure from Geobacillus stearothermophilus (PDB ID 1ZIN) are used as templates. ZgHGPRT/AMPK model is complexed with Hyp, PRPP and Mg2+ in the active site of the HGPRT domain, and with AMP, ATP and Mg2+ in the active site of AMPK domain. Essential elements of type I PRTs architecture are found in ZgHGPRT/AMPK amino acid sequence such as diphosphate loop, the flexible loop and PRPP binding domain (including PRPP loop), as well as in the homology model
additional information
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identification of a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK). ZgHGPRT/AMPK single domain, dual domain 3D structure homology modeling, HGPRT from Leptospira interrogans (PDB ID 4QRI) and AMPK structure from Geobacillus stearothermophilus (PDB ID 1ZIN) are used as templates. ZgHGPRT/AMPK model is complexed with Hyp, PRPP and Mg2+ in the active site of the HGPRT domain, and with AMP, ATP and Mg2+ in the active site of AMPK domain. Essential elements of type I PRTs architecture are found in ZgHGPRT/AMPK amino acid sequence such as diphosphate loop, the flexible loop and PRPP binding domain (including PRPP loop), as well as in the homology model
additional information
isozyme HPGRT-1 structure determination and analysis, active site structure, detailed overview
additional information
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isozyme HPGRT-1 structure determination and analysis, active site structure, detailed overview
additional information
out of the five active site loops (I, II, III, III', and IV) in PfHGXPRT, loop III' facilitates the closure of the hood over the core domain which is the penultimate step during enzymatic catalysis. Residue Trp181 is important. Molceluar dynamics and simulation, structure-activity analysis, overview
additional information
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out of the five active site loops (I, II, III, III', and IV) in PfHGXPRT, loop III' facilitates the closure of the hood over the core domain which is the penultimate step during enzymatic catalysis. Residue Trp181 is important. Molceluar dynamics and simulation, structure-activity analysis, overview
additional information
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identification of a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK). ZgHGPRT/AMPK single domain, dual domain 3D structure homology modeling, HGPRT from Leptospira interrogans (PDB ID 4QRI) and AMPK structure from Geobacillus stearothermophilus (PDB ID 1ZIN) are used as templates. ZgHGPRT/AMPK model is complexed with Hyp, PRPP and Mg2+ in the active site of the HGPRT domain, and with AMP, ATP and Mg2+ in the active site of AMPK domain. Essential elements of type I PRTs architecture are found in ZgHGPRT/AMPK amino acid sequence such as diphosphate loop, the flexible loop and PRPP binding domain (including PRPP loop), as well as in the homology model
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additional information
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identification of a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK). ZgHGPRT/AMPK single domain, dual domain 3D structure homology modeling, HGPRT from Leptospira interrogans (PDB ID 4QRI) and AMPK structure from Geobacillus stearothermophilus (PDB ID 1ZIN) are used as templates. ZgHGPRT/AMPK model is complexed with Hyp, PRPP and Mg2+ in the active site of the HGPRT domain, and with AMP, ATP and Mg2+ in the active site of AMPK domain. Essential elements of type I PRTs architecture are found in ZgHGPRT/AMPK amino acid sequence such as diphosphate loop, the flexible loop and PRPP binding domain (including PRPP loop), as well as in the homology model
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additional information
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crystals of enzyme-diphosphate-GMP complex are used for structure determination, detailed overview
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additional information
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crystals of enzyme-diphosphate-GMP complex are used for structure determination, detailed overview
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additional information
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identification of a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK). ZgHGPRT/AMPK single domain, dual domain 3D structure homology modeling, HGPRT from Leptospira interrogans (PDB ID 4QRI) and AMPK structure from Geobacillus stearothermophilus (PDB ID 1ZIN) are used as templates. ZgHGPRT/AMPK model is complexed with Hyp, PRPP and Mg2+ in the active site of the HGPRT domain, and with AMP, ATP and Mg2+ in the active site of AMPK domain. Essential elements of type I PRTs architecture are found in ZgHGPRT/AMPK amino acid sequence such as diphosphate loop, the flexible loop and PRPP binding domain (including PRPP loop), as well as in the homology model
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additional information
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identification of a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK). ZgHGPRT/AMPK single domain, dual domain 3D structure homology modeling, HGPRT from Leptospira interrogans (PDB ID 4QRI) and AMPK structure from Geobacillus stearothermophilus (PDB ID 1ZIN) are used as templates. ZgHGPRT/AMPK model is complexed with Hyp, PRPP and Mg2+ in the active site of the HGPRT domain, and with AMP, ATP and Mg2+ in the active site of AMPK domain. Essential elements of type I PRTs architecture are found in ZgHGPRT/AMPK amino acid sequence such as diphosphate loop, the flexible loop and PRPP binding domain (including PRPP loop), as well as in the homology model
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additional information
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identification of a putative dual-domain hypoxanthine-guanine phosphoribosyltransferase (HGPRT)/adenylate kinase (AMPK). ZgHGPRT/AMPK single domain, dual domain 3D structure homology modeling, HGPRT from Leptospira interrogans (PDB ID 4QRI) and AMPK structure from Geobacillus stearothermophilus (PDB ID 1ZIN) are used as templates. ZgHGPRT/AMPK model is complexed with Hyp, PRPP and Mg2+ in the active site of the HGPRT domain, and with AMP, ATP and Mg2+ in the active site of AMPK domain. Essential elements of type I PRTs architecture are found in ZgHGPRT/AMPK amino acid sequence such as diphosphate loop, the flexible loop and PRPP binding domain (including PRPP loop), as well as in the homology model
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