2.4.2.8: hypoxanthine phosphoribosyltransferase
This is an abbreviated version!
For detailed information about hypoxanthine phosphoribosyltransferase, go to the full flat file.
Word Map on EC 2.4.2.8
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2.4.2.8
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hamster
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lymphocyte
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genotoxic
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lesch-nyhan
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6-thioguanine
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salvage
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x-linked
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ovary
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gapdh
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adduct
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erythrocyte
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normfinder
-
nucleoside
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genorm
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thymidine
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housekeeping
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t-lymphocytes
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uric
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x-chromosome
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lymphoblast
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lymphoblastoid
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tbp
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micronuclei
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bestkeeper
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transversions
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chromatid
-
hyperuricemia
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gout
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benzoapyrene
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cytogenetic
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phosphoribosylpyrophosphate
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ywhaz
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comet
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allopurinol
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clastogenic
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n-ethyl-n-nitrosourea
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aminopterin
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mutable
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non-transcribed
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1,3-butadiene
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lns
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repair-deficient
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sister-chromatid
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32p-postlabeling
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x-ray-induced
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repair-proficient
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analysis
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pharmacology
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o6-methylguanine
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micronucleated
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synthesis
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drug development
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diagnostics
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biotechnology
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molecular biology
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butadiene
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x-inactivation
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medicine
- 2.4.2.8
- hamster
- lymphocyte
-
genotoxic
- lesch-nyhan
- 6-thioguanine
-
salvage
-
x-linked
- ovary
- gapdh
- adduct
- erythrocyte
-
normfinder
- nucleoside
-
genorm
- thymidine
-
housekeeping
- t-lymphocytes
-
uric
-
x-chromosome
- lymphoblast
-
lymphoblastoid
- tbp
-
micronuclei
-
bestkeeper
-
transversions
-
chromatid
- hyperuricemia
- gout
-
benzoapyrene
-
cytogenetic
-
phosphoribosylpyrophosphate
-
ywhaz
- comet
- allopurinol
-
clastogenic
-
n-ethyl-n-nitrosourea
- aminopterin
-
mutable
-
non-transcribed
- 1,3-butadiene
- lns
-
repair-deficient
-
sister-chromatid
-
32p-postlabeling
-
x-ray-induced
-
repair-proficient
- analysis
- pharmacology
- o6-methylguanine
-
micronucleated
- synthesis
- drug development
- diagnostics
- biotechnology
- molecular biology
- butadiene
-
x-inactivation
- medicine
Reaction
Synonyms
6-hydroxypurine phosphoribosyltransferase, 6-mercaptopurine phosphoribosyltransferase, 6-oxo PRTase, 6-oxopurine phosphoribosyltransferase, 6-oxopurine PRTase, Cthe_2254, EcHPRT, GMP pyrophosphorylase, GPRT, gpT-2, guanine phosphoribosyltransferase, guanine PRTase, guanine-hypoxanthine phosphoribosyltransferase, guanosine 5'-phosphate pyrophosphorylase, guanosine phosphoribosyltransferase, guanylate pyrophosphorylase, guanylic pyrophosphorylase, HGPRT, HGPRT-1, HGPRTase, HGXPRT, HGXPRTase, HG[X]PRT, HPRT, HPRT1, HPRTJerusalem, HPT, HXGPRT, hypoxanthine guanine phosphoribosyltransferase, hypoxanthine guanine xanthine phosphoribosyltransferase, hypoxanthine phosphoribosyl transferase, hypoxanthine phosphoribosyltransferase, hypoxanthine phosphoribosyltransferase 1, hypoxanthine PRTase, hypoxanthine-guanine phosphoribosyl transferase, hypoxanthine-guanine phosphoribosyltransferase, hypoxanthine-guanine phosphoribosyltransferase/adenylate kinase, hypoxanthine-guanine-(xanthine) phosphoribosyltransferase, hypoxanthine-guanine-xanthine phosphoribosyltransferase, hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase, hypoxanthine-xanthine-guanine phosphoribosyltransferase, IMP pyrophosphorylase, IMP-GMP pyrophosphorylase, inosinate pyrophosphorylase, inosine 5'-phosphate pyrophosphorylase, inosine monophosphate:pyrophosphate phosphoribosyltransferase, inosinic acid pyrophosphorylase, inosinic pyrophosphorylase, More, MSMEG_6110, MtHGPRT, Pf HGXPRT, PF3D7_1012400, PfHGXPRT, PhHGXPRT, phosphoribosyltransferase, 6-mercaptopurine, phosphoribosyltransferase, hypoxanthine, PhPRT, plasma hypoxanthine-guanine phosphoribosyl transferase, PRT, purine-6-thiol phosphoribosyltransferase, PvHGPRT, SmHGPRT1, SSO2424, Tb927.10.1400, TcHPRT, transphosphoribosidase, TthHPRT, TT_C1766, ZgHGPRT/AMPK
ECTree
2.4.2.8 hypoxanthine phosphoribosyltransferaseAdvanced search results
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Engineering on EC 2.4.2.8 - hypoxanthine phosphoribosyltransferase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
L160I
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site-directed mutagenesis, crystal structure determination
A72G
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site-directed mutagenesis, exchange in diphosphate binding site, decreased Km-value for diphosphate and guanine, increased Km-value for 5-phosphoribosyl 1-diphosphate, reduced activity
T70K
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site-directed mutagenesis, exchange in diphosphate binding site, 6.7fold lower Km-value for diphosphate, lower Km for guanine, 2fold increase in Km-value for 5-phosphoribosyl 1-diphosphate, reduced activity
T70K/A72G
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site-directed mutagenesis, exchange in diphosphate binding site, decreased Km-value for diphosphate and guanine, increased Km-value for 5-phosphoribosyl 1-diphosphate, reduced activity
A192V
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
A64P
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
C105A
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prepared via splicing by overlap extension, reduced oxidation ofthe enzyme during storage
C205A
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prepared via splicing by overlap extension, reduced oxidation ofthe enzyme during storage
C22A
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prepared via splicing by overlap extension, reduced oxidation ofthe enzyme during storage
C22A/C105A/C205A
C23F
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
D185G
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
D31E
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identification of another genetic variation within the gout-affected population in Taiwan with mutation on exon 2 with T to G transition at cDNA base 93 resulting in a change from aspartic acid to glutamic acid at position 31
D44V
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
E196A
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site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
E196D
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site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
E196Q
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site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
E196R
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site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
F199C
a naturally occuring mutation T596G, leads to 8% residual HPRT activity and causes juvenile-onset, severe gouty arthritis, nephrolithiasis, and mild neurologic symptoms. Adenine phosphoribosyltransferase, APRT, EC 2.4.2.7, in erythrocytes from subjects with HPRT deficiency is typically increased about 23fold compared with controls. Modeling of the mutated protein for prediction of the mechanisms of partial enzymatic activity
F36A
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
F36E
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
F36K
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
F36L
F36W
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
G140D
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
G70E
G70R
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
H204X
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
H60R
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naturally occuring mutation of HPRT1 gene, causes no altered phenotype compared to the wild-type enzyme
I137T
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DNA sequence determination and identification of the naturally occurring point mutation in the conserved 5-phosphoribosyl-1-diphosphate binding motif, causing a variant of Lesch-Nyhan syndrome, the mutation affects the affinity of the enzyme for 5-phosphoribosyl-1-diphosphate through structural alterations
I9S
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
K159E
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
L147F
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natural occuring point mutation leading to enzyme deficiency, which is not correlated with a physiological syndrome
L147P
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
L65P
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
L68P
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naturally occuring mutation in an Argentine individual, the patient shows the LND phenotype, determination of the altered urine purine alkaloid metabolite contents
L68R
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naturally occuring mutation in an Argentine individual, the patient shows the LND phenotype, determination of the altered urine purine alkaloid metabolite contents
L78Q
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
M54L
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
P24R
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
P25T
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
Q144X
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naturally occuring nonsense mutation of HPRT1 gene, exchange of 430C-T, causes the Lesch-Nyhan syndrome
R48H
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naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
R51X
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
S162R
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
T124P
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
T139P
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
V158G
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
V188A
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
Y195C
Y195S
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naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
Y72C
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
S103R
the mutation is associated with Gout arthritis and shows strongly reduced activity compared to the wild type enzyme
S95A
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site-directed mutagenesis, dramatic reduction of catalytic activity, weak complementation of bacterial enzyme deficient strain
S95C
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site-directed mutagenesis, 2-3fold reduction of kcat, weak complementation of bacterial enzyme deficient strain
S95E
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site-directed mutagenesis, dramatic reduction of catalytic activity, no complementation of bacterial enzyme deficient strain
S95T
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site-directed mutagenesis, 2-3fold reduction of kcat, complementation of bacterial enzyme deficient strain
Y96F
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site-directed mutagenesis, dramatic reduction of catalytic activity, no complementation of bacterial enzyme deficient strain, 4-5fold decrease of Km value for 5-phosphoribosyl 1-diphosphate
Y96V
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site-directed mutagenesis, dramatic reduction of catalytic activity, no complementation of bacterial enzyme deficient strain, 4-5fold decrease of Km value for 5-phosphoribosyl 1-diphosphate
F197W
the mutant shows reduced activity compared tot he wild type enzyme
L44F
W181F
site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 5fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)
W181S
site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 5fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)
W181S/F197W
the mutant shows reduced activity compared tot he wild type enzyme
W181T
site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 10fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)
W181Y
site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 5fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)
D150A
reduced activity compared to wild-type, kcat for hypoxanthine, guanine, and xanthine are reduced by 11fold, 296fold, and 8.6fold, respectively, Km value for alpha-D-5-phosphoribosyl 1-diphosphate is reduced by 6.5fold
D163E
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site directed mutagenesis, slightly changed substrate affinities compared to wild-type
D163N
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site-directed mutagensis, exchange of xanthine binding residue, loss of the binding ability and activity against xanthine and XMP
I104G
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site directed mutagenesis, increased Km values for hypoxanthine, guanine, and xanthine
K134Q
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site directed mutagenesis, mutant recognizes adenine as substrate in addition, but less efficient than mutant K134S
K134S
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site directed mutagenesis, mutant recognizes adenine as substrate in addition, increased Km values for hypoxanthine, guanine, and xanthine
R155E
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site directed mutagenesis, reduced affinity to GMP and XMP, catalysation of the forward reaction with guanine and xanthine at accelerated rates, 15fold increased Km for xanthine
R155K
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site directed mutagenesis, reduced affinity to GMP and XMP, catalysation of the forward reaction with guanine and xanthine at accelerated rates, insensitive to phenylglyoxal
T47K
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site-directed mutagenesis, exchange of diphosphate binding site residue, 4-10fold decreased Km for diphosphate compared to the wild-type
Y156W
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site directed mutagenesis, slightly changed substrate affinities compared to wild-type
L67M
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highly reduced activity with hypoxanthine compared to the wild-type enzyme, mutant is not active with guanine
additional information
C22A/C105A/C205A
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site-directed mutagenesis, kinetic and physical properties are similar to the wild-type enzyme, but the mutant enzyme is more resistant to oxidation
C22A/C105A/C205A
site-directed mutagenesis, the exchanges stabilize the enzyme protein, but kinetic and structural properties of the mutant enzyme are identical to wild-type human HGPRT
F36L
random mutagenesis, mutant phosphoribosylates xanthine, mutant does not bind the purine substrate directly, long-range modulation via loop IV influence the substrate specificity, altered enzyme stability
F36L
wild-type human enzyme does not accept xanthine as substrate, mutant F36L does catalyze the conversion of xanthine to XMP with a kcat much lower than those of hypoxanthine and guanine and fails to perturb the pKa of XMP
G70E
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naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
G70E
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
Y195C
-
naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
Y195C
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
L44F
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site-directed mutagenesis, mutant does not phosphoribosylate guanine and xanthine, modulation via loop IV influence the substrate specificity, altered enzyme stability
L44F
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site-directed mutagenesis, temperature-sensitive mutant, no complementation of an enzyme-deficient Escherichia coli strain at 42°C, only at 20°C and 37°C
additional information
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random enzyme mutations induced by neutron irradiation of CHO cells, analysis of the molecular structure of the HPRT mutations and the types of point mutations using direct sequencing of PCR fragments , overview
additional information
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construction of 4 chimeric enzymes with segments of human and Plasmodium falciparum enzymes, altered substrate specificities
additional information
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determination of the frequency of HPRT deficiency within the gout-affected population in Taiwan, overview
additional information
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induction of HPRT mutations in G0 peripheral blood lymphocytes exposed in vitro to gamma rays at low, 0.0014 Gy/min, and high, 0.85 Gy/min, dose rates, the mutation increases at both high and low radiation rates, dose-rate effect on the induced HPRT mutant frequency correlating inversely with the cell curvival, overview
additional information
construction of a chimera of Plasmodium falciparum and human HGPRTs, which consists of the core of the protein from the human enzyme and the hood region from the parasite enzyme. Replacement of Tyr197 of human HGPRT by Ile207 in the chimera disrupts the interaction at the AB interface in the absence of PRPP. In the presence of PRPP, the interaction between Pro93 and His26 can restore the AB interface, shifting the chimeric enzyme to a tetrameric state, active site structure, overview
additional information
-
construction of a chimera of Plasmodium falciparum and human HGPRTs, which consists of the core of the protein from the human enzyme and the hood region from the parasite enzyme. Replacement of Tyr197 of human HGPRT by Ile207 in the chimera disrupts the interaction at the AB interface in the absence of PRPP. In the presence of PRPP, the interaction between Pro93 and His26 can restore the AB interface, shifting the chimeric enzyme to a tetrameric state, active site structure, overview
additional information
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genotyping for mutations in the HPRT gene in healthy individuals and Lesch-Nyhan syndrome patients in Japanese population, diverse deletion mutations, detailed overview
additional information
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myosmine exhibits small, but significant, mutagenic potential and causes HPRT mutagenesis in nonsmoker lymphocytes, mutation frequency, overview
additional information
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shRNA knockdown of HPRT gene expression leading toloss of 94% activity, HPRT-deficient NT2 cells demonstrate aberrant expression of several transcription factors and dopaminergic markers
additional information
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wild-type enzyme complements enzyme deficiency of the bacterial enzyme in Escherichia coli
additional information
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construction of mutant lacking the Ser-Lys-Val C-terminal targeting signal, mutant enzyme is located throughout the parasite, including subcellular organelles such as nucleus and flagellum
additional information
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generation of HPRT gene knock-out mice, the mutant mice show 55% increased expression of the serotonin receptor 2C, HTR2C, semiquantitative realtime RT-PCR expression analysis
additional information
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construction of 4 chimeric enzymes with segments of human and Plasmodium falciparum enzymes, altered substrate specificities
additional information
construction of a chimera of Plasmodium falciparum and human HGPRTs, which consists of the core of the protein from the human enzyme and the hood region from the parasite enzyme. Replacement of Tyr197 of human HGPRT by Ile207 in the chimera disrupts the interaction at the AB interface in the absence of PRPP. In the presence of PRPP, the interaction between Pro93 and His26 can restore the AB interface, shifting the chimeric enzyme to a tetrameric state, active site structure, overview
additional information
-
construction of a chimera of Plasmodium falciparum and human HGPRTs, which consists of the core of the protein from the human enzyme and the hood region from the parasite enzyme. Replacement of Tyr197 of human HGPRT by Ile207 in the chimera disrupts the interaction at the AB interface in the absence of PRPP. In the presence of PRPP, the interaction between Pro93 and His26 can restore the AB interface, shifting the chimeric enzyme to a tetrameric state, active site structure, overview
additional information
molecular dynamics simulations of wild-type and in silico W181S, W181T, W181Y, and W181F PfHGXPRT mutants bound to IMP/PPi/Mg2+, overview. Escherichia coli strain Sphi609, (ara, DELTApro-gpt-lac, thi, hpt, pup, purH, J, strA) is a knockout strain for the genes encoding hypoxanthine phosphoribosyltransferase (HPRT) and xanthine-guanine phosphoribosyltransferase (XGPRT). Although activation of the enzyme mutants by IMP increases their catalytic efficiency by about 100fold, it is found that the kcat/Km values for the mutants drop by 5.7 to 75fold when compared with the wild-type enzyme
additional information
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molecular dynamics simulations of wild-type and in silico W181S, W181T, W181Y, and W181F PfHGXPRT mutants bound to IMP/PPi/Mg2+, overview. Escherichia coli strain Sphi609, (ara, DELTApro-gpt-lac, thi, hpt, pup, purH, J, strA) is a knockout strain for the genes encoding hypoxanthine phosphoribosyltransferase (HPRT) and xanthine-guanine phosphoribosyltransferase (XGPRT). Although activation of the enzyme mutants by IMP increases their catalytic efficiency by about 100fold, it is found that the kcat/Km values for the mutants drop by 5.7 to 75fold when compared with the wild-type enzyme
additional information
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chimeric constructs expressing N-terminal peptides of 11 amino acids from isoform I or of 60 amino acids from isoform II fused to a chloramphenicol acetyl transferase reporter show that the N-terminal domain of isoform II is both necessary and sufficient for membrane association
additional information
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construction of deletion mutant lacking 7 amino acid residues, Y82-S88, of the active site loop II, resulting in highly reduced kcat-values and in increased Km-values for the substrates
additional information
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saturation mutagenesis and complement selection for investigation of functional roles of residues Leu67 and Gly69, sequencing of 70 clones and identification of 30 different mutations, several mutants of L67 or G69 support bacterial growth on minimal medium, but only L67M and G69S can be expressed and purified from overexpressing bacteria, overview
additional information
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saturation mutagenesis for randomly exchange of amino acids of the active site loop II, construction of diverse mutants of the residues S102 to Q112, kinetic analysis and determination of catalytic efficiencies in the forward and reverse reaction, overview
additional information
truncation of the C-terminal stretch of enzyme TcHPRTH6 enhances its catalytic efficiency
additional information
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truncation of the C-terminal stretch of enzyme TcHPRTH6 enhances its catalytic efficiency
