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evolution
adenine phosphoribosyltransferase (APRT) from the thermophilic eubacteria Thermus thermophilus belongs to the type I phosphorybosyltransferase protein family on the basis of its structure and catalytic activity
evolution
APRT refers to the type I phosphoribosyltransferase (PRT) family, which belongs to the large glycosyltransferase family
evolution
the TTC1250 gene encoding APRT, has 41% amino acid sequence identity to gene TTC1249 encoding APRTh, an catalytically inactve APRT homologue
evolution
the TTC1250 gene, which also encodes APRT, has 41% amino acid sequence identity to gene TTC1249 encoding APRTh
evolution
Thermus thermophilus strain HB27 enzyme TthHB27APRT belongs to the type I phosphoribosyltransferases. These share the alpha/beta type folding of the polypeptide chain and the presence of a specific sequence of 13 amino acid residues involved in binding of diphosphate (PRPP-binding motif), together with a structurally variable subdomain (the so-called, hood domain) involved in base recognition
evolution
three putative APRT isoforms are described in the genome of Schistosoma mansoni, namely, Smp_054360, Smp_054410, and Smp_151260, which are referred to as SmAPRT 1, 2 and 3, respectively. Phylogenetic analysis reveals that APRT exists in multiple copies originating from gene duplications at the base of the Schistosoma genus
evolution
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the TTC1250 gene encoding APRT, has 41% amino acid sequence identity to gene TTC1249 encoding APRTh, an catalytically inactve APRT homologue
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evolution
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adenine phosphoribosyltransferase (APRT) from the thermophilic eubacteria Thermus thermophilus belongs to the type I phosphorybosyltransferase protein family on the basis of its structure and catalytic activity
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evolution
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Thermus thermophilus strain HB27 enzyme TthHB27APRT belongs to the type I phosphoribosyltransferases. These share the alpha/beta type folding of the polypeptide chain and the presence of a specific sequence of 13 amino acid residues involved in binding of diphosphate (PRPP-binding motif), together with a structurally variable subdomain (the so-called, hood domain) involved in base recognition
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evolution
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the TTC1250 gene, which also encodes APRT, has 41% amino acid sequence identity to gene TTC1249 encoding APRTh
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evolution
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the TTC1250 gene encoding APRT, has 41% amino acid sequence identity to gene TTC1249 encoding APRTh, an catalytically inactve APRT homologue
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evolution
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adenine phosphoribosyltransferase (APRT) from the thermophilic eubacteria Thermus thermophilus belongs to the type I phosphorybosyltransferase protein family on the basis of its structure and catalytic activity
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evolution
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Thermus thermophilus strain HB27 enzyme TthHB27APRT belongs to the type I phosphoribosyltransferases. These share the alpha/beta type folding of the polypeptide chain and the presence of a specific sequence of 13 amino acid residues involved in binding of diphosphate (PRPP-binding motif), together with a structurally variable subdomain (the so-called, hood domain) involved in base recognition
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evolution
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the TTC1250 gene, which also encodes APRT, has 41% amino acid sequence identity to gene TTC1249 encoding APRTh
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malfunction
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a congenital deficiency in the enzyme adenine phosphoribosyltransferase causes the disorder with 2,8-dihydroxyadenine crystalluria. In most cases, APRT deficiency is caused by autosomal recessive inheritance of a homozygote of the mutant gene APRT*Q0 or APRT*J, but there are also some cases in which the disorder is caused by the compound heterozygote APRT*Q0 and APRT*J
malfunction
loss of enzyme activity leads to excess accumulation of cytokinin bases, thus evoking myriad cytokinin-regulated responses, such as delayed leaf senescence, anthocyanin accumulation, and downstream gene expression
malfunction
APRT deficiencies in this enzyme lead to 2,8-dihydroxyadenine urolithiasis, and renal and allograft failures
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
adenine phosphoribosyl transferase 1 is a key metabolic enzyme participating in the cytokinin inactivation by phosphoribosylation
metabolism
APRT from Thermus thermophilus is a member of purine nucleotide processing methabolical pathways and can be used as a key component of an nucleotide synthesis enzymatic cascade that uses only pentose carbohydrates, nitrogenous bases and ATP as substrates
metabolism
APRT is an enzyme involved in the salvage of adenine (a 6-aminopurine), converting it to AMP. The purine salvage pathway relies on two essential and distinct enzymes to convert 6-aminopurine and 6-oxopurines into corresponding nucleotides
metabolism
enzyme APRT is a key enzyme in the purine salvage pathway in prokaryotes and eukaryotes
metabolism
the reversible adenine phosphoribosyltransferase enzyme (APRT) is essential for purine homeostasis in prokaryotes and eukaryotes. In humans, APRT (hAPRT) is the only enzyme known to produce AMP in cells from dietary adenine. APRT can also process adenine analogues, which are involved in plant development or neuronal homeostasis
metabolism
type I phosphoribosyltransferases play an important role in common and salvage pathways of purine, pyrimidine, and pyrimidine coenzyme synthesis, as well as biosynthesis of histidine and tryptophan in lower organisms
metabolism
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APRT is an enzyme involved in the salvage of adenine (a 6-aminopurine), converting it to AMP. The purine salvage pathway relies on two essential and distinct enzymes to convert 6-aminopurine and 6-oxopurines into corresponding nucleotides
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metabolism
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APRT from Thermus thermophilus is a member of purine nucleotide processing methabolical pathways and can be used as a key component of an nucleotide synthesis enzymatic cascade that uses only pentose carbohydrates, nitrogenous bases and ATP as substrates
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metabolism
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type I phosphoribosyltransferases play an important role in common and salvage pathways of purine, pyrimidine, and pyrimidine coenzyme synthesis, as well as biosynthesis of histidine and tryptophan in lower organisms
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metabolism
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APRT from Thermus thermophilus is a member of purine nucleotide processing methabolical pathways and can be used as a key component of an nucleotide synthesis enzymatic cascade that uses only pentose carbohydrates, nitrogenous bases and ATP as substrates
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metabolism
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type I phosphoribosyltransferases play an important role in common and salvage pathways of purine, pyrimidine, and pyrimidine coenzyme synthesis, as well as biosynthesis of histidine and tryptophan in lower organisms
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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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amplification of adenine phosphoribosyltransferase suppresses the conditionally lethal growth and virulence phenotype of Leishmania donovani mutants lacking both hypoxanthine-guanine and xanthine phosphoribosyltransferases. Transfection of mutants lacking both hypoxanthine-guanine and xanthine phosphoribosyltransferases with an adenine phosphoribosyltransferase episome recapitulates the suppressor phenotype in vitro and enables growth on 6-oxypurines. Hypoxanthine is an inefficient substrate for adenine phosphoribosyltransferase
physiological function
adenine phosphoribosyltransferase (APRT) belongs to the type I phosphoribosyltransferases and catalyzes the formation of adenosine monophosphate via transfer of the 5-phosphoribosyl group from phosphoribosyl diphosphate to the nitrogen atom N9 of the adenine base
physiological function
adenine phosphoribosyltransferase, APRT catalyzes the transfer of the 5-phosphoribosyl group from 5-phospho-alpha-D-ribosyl-1-diophosphate (PRPP) to N9 in 6-aminopurines, such as adenine or 6-aminopurine derivatives (e.g. 2,6-diaminopurine, 6-methylpurine, 2-fluoroadenine, among others), in presence of Mg2+ to obtain the corresponding NMPs
physiological function
APRT is the sole enzyme with the crucial role of recycling (or salvaging) freely available adenine into AMP and exists in all phyla of life
physiological function
enzyme adenine phosphoribosyltransferase homologue occurs in complex with Thermus thermophilus glutamate dehydrogenase. APRTh mediates the allosteric activation of GDH by AMP, but shows no adenine phosphoribosyltransferase activity. Presence of complicated regulatory mechanisms of GDH mediated by multiple compounds to control the carbonnitrogen balance in bacterial cells. APRTh functions in the cell and supports the optimal growth of Thermus thermophilus in minimal medium
physiological function
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expression and role of adenine phosphoribosyltransferase (APRT) in Trypanosoma cruzi resistance to benznidazole (Bz), overview
physiological function
phosphoribosyltransferases catalyze the displacement of a PRPP alpha-1'-diphosphate to a nitrogen-containing nucleobase. Phosphoribosyltransferase APRT residue Tyr105 is essential for cell growth by facilitating the forward reaction, The APRT Tyr105 drives purine biosynthesis in vivo. Tyr105 is key for the fine-tuning of the kinetic activity efficiencies of forward and reverse reactions. In crystallo activity shows that the hydroxyl group of Tyr105 is essential to select the bioactive conformation of the dynamic flexible loop and to form the products
physiological function
purine phosphoribosyltransferases, purine PRTs, are essential enzymes in the purine salvage pathway of living organisms. They are involved in the formation of C-N glycosidic bonds in purine nucleosides-5'-monophosphate (NMPs) through the transfer of the 5-phosphoribosyl group from 5-phospho-alpha-D-ribosyl-1-diphosphate (PRPP) to purine nucleobases in the presence of Mg2+
physiological function
Schistosoma mansoni depends upon the purine salvage pathway to obtain purine nucleotides. Therefore, enzymes from this pathway are essential for parasite survival, e.g. the adenine phosphoribosyltransferase (APRT) enzyme, which catalyzes the condensation reaction between adenine and PRPP (5-phosphoribosyldiphosphate) to produce AMP and PPi
physiological function
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expression and role of adenine phosphoribosyltransferase (APRT) in Trypanosoma cruzi resistance to benznidazole (Bz), overview
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physiological function
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APRT is the sole enzyme with the crucial role of recycling (or salvaging) freely available adenine into AMP and exists in all phyla of life
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physiological function
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adenine phosphoribosyltransferase (APRT) belongs to the type I phosphoribosyltransferases and catalyzes the formation of adenosine monophosphate via transfer of the 5-phosphoribosyl group from phosphoribosyl diphosphate to the nitrogen atom N9 of the adenine base
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physiological function
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enzyme adenine phosphoribosyltransferase homologue occurs in complex with Thermus thermophilus glutamate dehydrogenase. APRTh mediates the allosteric activation of GDH by AMP, but shows no adenine phosphoribosyltransferase activity. Presence of complicated regulatory mechanisms of GDH mediated by multiple compounds to control the carbonnitrogen balance in bacterial cells. APRTh functions in the cell and supports the optimal growth of Thermus thermophilus in minimal medium
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physiological function
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expression and role of adenine phosphoribosyltransferase (APRT) in Trypanosoma cruzi resistance to benznidazole (Bz), overview
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physiological function
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expression and role of adenine phosphoribosyltransferase (APRT) in Trypanosoma cruzi resistance to benznidazole (Bz), overview
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physiological function
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purine phosphoribosyltransferases, purine PRTs, are essential enzymes in the purine salvage pathway of living organisms. They are involved in the formation of C-N glycosidic bonds in purine nucleosides-5'-monophosphate (NMPs) through the transfer of the 5-phosphoribosyl group from 5-phospho-alpha-D-ribosyl-1-diphosphate (PRPP) to purine nucleobases in the presence of Mg2+
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physiological function
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adenine phosphoribosyltransferase, APRT catalyzes the transfer of the 5-phosphoribosyl group from 5-phospho-alpha-D-ribosyl-1-diophosphate (PRPP) to N9 in 6-aminopurines, such as adenine or 6-aminopurine derivatives (e.g. 2,6-diaminopurine, 6-methylpurine, 2-fluoroadenine, among others), in presence of Mg2+ to obtain the corresponding NMPs
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physiological function
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purine phosphoribosyltransferases, purine PRTs, are essential enzymes in the purine salvage pathway of living organisms. They are involved in the formation of C-N glycosidic bonds in purine nucleosides-5'-monophosphate (NMPs) through the transfer of the 5-phosphoribosyl group from 5-phospho-alpha-D-ribosyl-1-diphosphate (PRPP) to purine nucleobases in the presence of Mg2+
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physiological function
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adenine phosphoribosyltransferase, APRT catalyzes the transfer of the 5-phosphoribosyl group from 5-phospho-alpha-D-ribosyl-1-diophosphate (PRPP) to N9 in 6-aminopurines, such as adenine or 6-aminopurine derivatives (e.g. 2,6-diaminopurine, 6-methylpurine, 2-fluoroadenine, among others), in presence of Mg2+ to obtain the corresponding NMPs
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physiological function
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adenine phosphoribosyltransferase (APRT) belongs to the type I phosphoribosyltransferases and catalyzes the formation of adenosine monophosphate via transfer of the 5-phosphoribosyl group from phosphoribosyl diphosphate to the nitrogen atom N9 of the adenine base
-
physiological function
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enzyme adenine phosphoribosyltransferase homologue occurs in complex with Thermus thermophilus glutamate dehydrogenase. APRTh mediates the allosteric activation of GDH by AMP, but shows no adenine phosphoribosyltransferase activity. Presence of complicated regulatory mechanisms of GDH mediated by multiple compounds to control the carbonnitrogen balance in bacterial cells. APRTh functions in the cell and supports the optimal growth of Thermus thermophilus in minimal medium
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additional information
analysis of the molecular mechanism underlying substrate specificity of APRT and catalysis in both directions of the reaction. Comparison of the crystal structures of hAPRT complexed to three cellular nucleotide analogues (hypoxanthine, IMP, and GMP) with the phosphate-bound enzyme. Substrate shape recognition in the forward reaction, purine base recognition in the reverse reaction. Binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction. Quantum mechanics/molecular mechanics (QM/MM) analysis suggests that the forward reaction is mainly a nucleophilic substitution of type 2 (SN2) with a mix of SN1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted SN2-type mechanism is involved in the reverse reaction. Structure-function analysis, overview
additional information
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analysis of the molecular mechanism underlying substrate specificity of APRT and catalysis in both directions of the reaction. Comparison of the crystal structures of hAPRT complexed to three cellular nucleotide analogues (hypoxanthine, IMP, and GMP) with the phosphate-bound enzyme. Substrate shape recognition in the forward reaction, purine base recognition in the reverse reaction. Binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction. Quantum mechanics/molecular mechanics (QM/MM) analysis suggests that the forward reaction is mainly a nucleophilic substitution of type 2 (SN2) with a mix of SN1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted SN2-type mechanism is involved in the reverse reaction. Structure-function analysis, overview
additional information
modeling of the model of the enzyme, substrate and magnesium cation co-factor complex and structure-function relationship analysis, X-ray crystallographic and NMR structure analysis, overview. In silico modeling of protein-ligand interaction by molecular docking via simulations of molecular dynamic, modeling of the APRT-PRPP-Mg2+ enzyme complex, homology modeling using the APRT structure from Homo sapiens (PDB code 1ZN7)
additional information
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modeling of the model of the enzyme, substrate and magnesium cation co-factor complex and structure-function relationship analysis, X-ray crystallographic and NMR structure analysis, overview. In silico modeling of protein-ligand interaction by molecular docking via simulations of molecular dynamic, modeling of the APRT-PRPP-Mg2+ enzyme complex, homology modeling using the APRT structure from Homo sapiens (PDB code 1ZN7)
additional information
structure analysis and comparisons, detailed overview
additional information
the base-binding loop is stabilized by a cluster of aromatic and conformation-restricting proline residues, and (b) an N-H-N hydrogen bond between the base-binding loop and the N1 atom of adenine is the key interaction that differentiates adenine from 6-oxopurines. The residues conferring rigidity to the base-binding loop are highly conserved. Comparison of structure and sequences of APRTs from the Trypanosomatidae family with a destabilizing insertion on the base-binding loop and propose the mechanism by which these evolutionarily divergent enzymes achieve base specificity. The base-binding loop not only confers appropriate affinity but also provides defined specificity for adenine. FtAPRT structure is divided into (a) the base-binding domain, (b) the core PRPP binding domain and (c) a flexible catalytic loop, which is proposed to sequester the active site from the solvent at the time of catalysis. Enzyme residue F23 is a key residue that stacks with the F16-P17 cis-peptide pair and stabilizes the base-binding loop. This residue also plays an important role by stacking against the substrate adenine
additional information
the hydroxyl group in conserved tyrosine 105 controls the protein dynamics and the catalytic efficiencies of the forward and reverse reactions. Determination of the key residues of the reaction and the catalytic flexible loop dynamics. Tyr105 is essential for cell growth by facilitating the forward reaction. The active site of APRT consists of a 13-amino-acid-long PRPP-binding motif, starting from Val123 in hAPRT, with a conserved A131TGGS/T core sequence which serves to anchor the 5'-monophosphate group of either PRPP or ribonucleotides. It also contains two adjacent aspartates (Asp127 and Asp128 in hAPRT), two arginines (Arg67 and Arg87), and a specific cis-peptide bond, between Asp65 and Ser66, which hold together the 2'- and 3'-OH of the ribose and the diphosphate moiety of PRPP. Analysis of the role of hAPRT flexible loop
additional information
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the hydroxyl group in conserved tyrosine 105 controls the protein dynamics and the catalytic efficiencies of the forward and reverse reactions. Determination of the key residues of the reaction and the catalytic flexible loop dynamics. Tyr105 is essential for cell growth by facilitating the forward reaction. The active site of APRT consists of a 13-amino-acid-long PRPP-binding motif, starting from Val123 in hAPRT, with a conserved A131TGGS/T core sequence which serves to anchor the 5'-monophosphate group of either PRPP or ribonucleotides. It also contains two adjacent aspartates (Asp127 and Asp128 in hAPRT), two arginines (Arg67 and Arg87), and a specific cis-peptide bond, between Asp65 and Ser66, which hold together the 2'- and 3'-OH of the ribose and the diphosphate moiety of PRPP. Analysis of the role of hAPRT flexible loop
additional information
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Trypanosoma cruzi regulation is mainly posttranscriptional
additional information
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Trypanosoma cruzi regulation is mainly posttranscriptional
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additional information
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the base-binding loop is stabilized by a cluster of aromatic and conformation-restricting proline residues, and (b) an N-H-N hydrogen bond between the base-binding loop and the N1 atom of adenine is the key interaction that differentiates adenine from 6-oxopurines. The residues conferring rigidity to the base-binding loop are highly conserved. Comparison of structure and sequences of APRTs from the Trypanosomatidae family with a destabilizing insertion on the base-binding loop and propose the mechanism by which these evolutionarily divergent enzymes achieve base specificity. The base-binding loop not only confers appropriate affinity but also provides defined specificity for adenine. FtAPRT structure is divided into (a) the base-binding domain, (b) the core PRPP binding domain and (c) a flexible catalytic loop, which is proposed to sequester the active site from the solvent at the time of catalysis. Enzyme residue F23 is a key residue that stacks with the F16-P17 cis-peptide pair and stabilizes the base-binding loop. This residue also plays an important role by stacking against the substrate adenine
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additional information
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modeling of the model of the enzyme, substrate and magnesium cation co-factor complex and structure-function relationship analysis, X-ray crystallographic and NMR structure analysis, overview. In silico modeling of protein-ligand interaction by molecular docking via simulations of molecular dynamic, modeling of the APRT-PRPP-Mg2+ enzyme complex, homology modeling using the APRT structure from Homo sapiens (PDB code 1ZN7)
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additional information
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structure analysis and comparisons, detailed overview
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additional information
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Trypanosoma cruzi regulation is mainly posttranscriptional
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additional information
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Trypanosoma cruzi regulation is mainly posttranscriptional
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additional information
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modeling of the model of the enzyme, substrate and magnesium cation co-factor complex and structure-function relationship analysis, X-ray crystallographic and NMR structure analysis, overview. In silico modeling of protein-ligand interaction by molecular docking via simulations of molecular dynamic, modeling of the APRT-PRPP-Mg2+ enzyme complex, homology modeling using the APRT structure from Homo sapiens (PDB code 1ZN7)
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additional information
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structure analysis and comparisons, detailed overview
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