Literature summary for 2.4.2.8 extracted from

Romanello, L.; Zeraik, A.E.; de Freitas Fernandes, A.; Torini, J.R.; Bird, L.E.; Nettleship, J.E.; Rada, H.; Reddivari, Y.; Owens, R.J.; Serrao, V.H.B.; DeMarco, R.; Brandao-Neto, J.; Pereira, H.D.
In vitro and in vivo characterization of the multiple isoforms of Schistosoma mansoni hypoxanthine-guanine phosphoribosyltransferases (2019), Mol. Biochem. Parasitol., 229, 24-34 .

Application

Application	Comment	Organism
medicine	the enzyme is an efficient antischistosomal chemotherapy target	Schistosoma mansoni

Cloned(Commentary)

Cloned (Comment)	Organism
gene HGPRT, sequence comparisons of HGPRT isozymes of Schistosoma mansoni, recombinant expression of His-tagged enzyme SmHGPRT1 in Escherichia coli strain Lemo21(DE3)	Schistosoma mansoni

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified isozyme HPGRT-1 in complex with IMP, 2,5 mg/ml enzyme and 2 mM of IMP are mixed with 12.5% PEG 1000, 12.5% PEG 3350, 12.5% MPD, 0.03 M divalent cations, and 0.1 M MES/imidazole, pH 6.5, at 18°C, X-ray diffraction structure determination and analysis at 2.8 A resolution, screening and method optimmization, HPGRT-1 crystallizes in an orthorhombic system, and the systematic absences indicates space group P212121 with four polypeptide chains in the asymmetric unit, respectively	Schistosoma mansoni

Crystallization (Comment)

Organism

purified isozyme HPGRT-1 in complex with IMP, 2,5 mg/ml enzyme and 2 mM of IMP are mixed with 12.5% PEG 1000, 12.5% PEG 3350, 12.5% MPD, 0.03 M divalent cations, and 0.1 M MES/imidazole, pH 6.5, at 18°C, X-ray diffraction structure determination and analysis at 2.8 A resolution, screening and method optimmization, HPGRT-1 crystallizes in an orthorhombic system, and the systematic absences indicates space group P212121 with four polypeptide chains in the asymmetric unit, respectively

Schistosoma mansoni

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
additional information	-	additional information	Michaelis-Menten kinetics	Schistosoma mansoni
0.029	-	guanine	pH 7.5, 37°C, recombinant isozyme HGPRT-1	Schistosoma mansoni
0.047	-	hypoxanthine	pH 7.5, 37°C, recombinant isozyme HGPRT-1	Schistosoma mansoni

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
guanine + 5-phospho-alpha-D-ribose 1-diphosphate	Schistosoma mansoni	-	GMP + diphosphate	-	?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate	Schistosoma mansoni	-	IMP + diphosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Schistosoma mansoni	P09383	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain Lemo21(DE3) by cobalt affinity chromatography	Schistosoma mansoni

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
guanine + 5-phospho-alpha-D-ribose 1-diphosphate	-	Schistosoma mansoni	GMP + diphosphate	-	?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate	-	Schistosoma mansoni	IMP + diphosphate	-	?

Subunits

Subunits	Comment	Organism
tetramer	the tetrameric oligomerization state is required for enzyme activity, since residues that make up the active site are also involved in interactions in the dimeric interface, guiding the invariable residue Arg206 toward the active site	Schistosoma mansoni

Synonyms

Synonyms	Comment	Organism
HGPRT	-	Schistosoma mansoni
HGPRT-1	-	Schistosoma mansoni
hypoxanthine-guanine phosphoribosyltransferase	-	Schistosoma mansoni
SmHGPRT1	-	Schistosoma mansoni

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Schistosoma mansoni

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Schistosoma mansoni

General Information

General Information	Comment	Organism
evolution	four substitutions are identified in the region of the active site between SmHGPRT and human HGPRT: Ile149Met, Pro176Arg, Val189Ile, and Arg192Lys	Schistosoma mansoni
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	Schistosoma mansoni
additional information	isozyme HPGRT-1 structure determination and analysis, active site structure, detailed overview	Schistosoma mansoni