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GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
XMP + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
-
-
r
allopurinol + 5-phospho-alpha-D-ribose 1-diphosphate
allopurinol ribonucleoside 5'-monophosphate + diphosphate
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
additional information
?
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
wild-type and chimeric mutant enzyme
modeling of GMP binding to the chimeric enzyme
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
wild-type and chimeric mutant enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
wild-type and chimeric mutant enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
r
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
a freely reversible Mg2+-dependent conversion
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
the enzyme is involved in the purine salvage pathway
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
a freely reversible Mg2+-dependent conversion
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
-
low activity
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
-
wild-type enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
recombinant chimeric mutant DS1
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
the enzyme also performs the reaction of xanthine phosphoribosyltransferase, EC 2.4.2.22
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
reaction of EC 2.4.2.22
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
reaction of EC 2.4.2.22
-
-
?
additional information
?
-
-
the enzyme activity is regulated by stabilization and destabilization of the enzyme through release or binding of product and substrates, overview
-
-
?
additional information
?
-
-
the purified recombinant enzyme shows very low activity
-
-
?
additional information
?
-
-
the parasite depends on the human host purine salvage pathway enzyme hypoxanthine guanine xanthine phosphoribosyltransferase for survival, because it does not have a de novo pathway for synthesis of nucleotides on its own
-
-
?
additional information
?
-
-
the binding site for the 5'-phosphate is located at residues 132-141
-
-
?
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GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
XMP + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
additional information
?
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
?
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
-
the enzyme is involved in the purine salvage pathway
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
-
low activity
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
-
wild-type enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
reaction of EC 2.4.2.22
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
-
reaction of EC 2.4.2.22
-
-
?
additional information
?
-
-
the enzyme activity is regulated by stabilization and destabilization of the enzyme through release or binding of product and substrates, overview
-
-
?
additional information
?
-
-
the parasite depends on the human host purine salvage pathway enzyme hypoxanthine guanine xanthine phosphoribosyltransferase for survival, because it does not have a de novo pathway for synthesis of nucleotides on its own
-
-
?
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
(3-hydroxy-2-[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]methyl]propyl)phosphonic acid
-
3-((7-hydroxy-1H-pyrazolo[4,3-d]pyrimidin-3-yl)methylamino)propylphosphonate
-
9-deazaguanine
uncompetitive inhibitor
GMP
competitive inhibitor with respect to guanine, xanthine, and 5-phospho-alpha-D-ribose 1-diphosphate
[(+/-)-2(R/S)-3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propoxy]phosphonic acid
-
[(+/-)-2(R/S)-[([2-chloro-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
-
[(2R)-2-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
-
[(2R)-3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propoxy]phosphonic acid
-
[(2S)-2-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
-
[(2S,3R)-2,4-dihydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butoxy]phosphonic acid
-
[(3R)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
-
[(3S)-1,1-difluoro-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
-
[(3S)-3-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-1,1-difluoro-4-hydroxybutyl]phosphonic acid
-
[(3S)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
-
[2-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propyl] phosphonic acid
-
[2-[(2-[4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]ethyl)amino]ethyl]phosphonic acid
-
[2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]ethoxy]phosphonic acid
-
[3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-2-(hydroxymethyl)propoxy]phosphonic acid
-
[3-[(2-[4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]ethyl)amino]propyl]phosphonic acid
-
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
-
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]ethyl]phosphonic acid
-
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]methyl]phosphonic acid
-
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]pentyl]phosphonic acid
-
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propyl]phosphonic acid
-
(1S)-1-(9-deazaguanin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol 5-phosphate
-
-
(1S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol 5-phosphate
-
-
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid
enzyme-bound crystal structure analysis
(2-[3-(8-bromoguanin-9-yl)-2-(2-(bishydroxyphosphoryl)-ethoxy)propoxy]ethyl)phosphonic acid
-
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid
-
(3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]propyl)phosphonic acid
-
competitive. 466fold lower affinity for human enzyme. Treatment of cultured parasites with the bis-pavalate of the inhibitor as a prodrug inhibits growth with an IC50 of 45 microM
(R)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
-
(R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-8-bromoguanine
-
-
(R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
is toxic to cells and arrests cell growth
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid
-
(S)-9-[2-(phosphonomethoxy)propyl]guanine
-
-
(S)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-8-azaguanine
-
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-8-bromoguanine
-
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
([2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-3-(2-phosphonoethoxy)propoxy]methyl)phosphonic acid
-
([2-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-3-(2-phosphonoethoxy)propoxy]methyl)phosphonic acid
-
([3-(7-deazaguanine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methyl)phosphonic acid
sodium salt
([3-(7-deazahypoxanthine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methyl)phosphonic acid
sodium salt
([3-(8-bromoguanine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methyl)phosphonic acid
sodium salt
([3-(8-bromohypoxanthine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methyl)phosphonic acid
sodium salt
([3-(guanine-9-yl)-2-((2-phosphonoethoxy)-methyl)propoxy]methyl)phosphonic acid
sodium salt
([3-(hypoxanthine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methyl)phosphonic acid
sodium salt
6-methylheptyl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
-
9-[2-(2-phosphonoethoxy)ethyl]guanine
-
-
9-[2-(2-phosphonoethoxy)ethyl]hypoxanthine
-
-
9-[2-(phosphonomethoxy)-3-fluoro-propyl]guanine
-
-
9-[2-(phosphonomethoxy)ethyl]-6-thioguanine
-
-
9-[2-(phosphonomethoxy)ethyl]-7-deaza-8-azahypoxanthine
-
-
9-[2-(phosphonomethoxy)ethyl]-8-azaguanine
-
-
9-[2-(phosphonomethoxy)ethyl]-8-bromoguanine
-
-
9-[2-(phosphonomethoxy)ethyl]guanine
9-[2-(phosphonomethoxy)ethy]-8-hydroxyguanine
-
-
acyclic nucleoside phosphonates
-
analogues of the nucleotide reaction product, comprising a purine base joined by a linker to a phosphonate moiety, inhibitor design and potencies, overview. Selectivity for the parasite enzyme of up to 58 compared to the Homo sapiens enzyme, overview, design of potent and selective acyclic nucleoside phosphonates inhibitors of Plasmodium falciparum HGXPRT as antimalarial drug leads
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
is toxic to cells and arrests cell growth
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
is toxic to cells and arrests cell growth
diethyl (2S,15S)-2,15-dibenzyl-4,13-bis[[(2S)-1-ethoxy-1-oxo-3-phenylpropan-2-yl]amino]-4,13-dioxo-8-[(4-oxo-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl]-6,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
prodrug
diethyl (2S,15S)-2,15-dibenzyl-4,13-bis[[(2S)-1-ethoxy-1-oxo-3-phenylpropan-2-yl]amino]-4,13-dioxo-8-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-6,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
prodrug
diethyl (2S,15S)-2,15-dibenzyl-8-[(8-bromo-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-4,13-bis[[(2S)-1-ethoxy-1-oxo-3-phenylpropan-2-yl]amino]-4,13-dioxo-6,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
prodrug
diethyl (2S,15S)-4,13-bis[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-4,13-dioxo-8-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-2,15-bis(2-phenylethyl)-6,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
-
diethyl (2S,15S)-8-[(2-amino-4-oxo-3,4-dihydro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl]-2,15-dibenzyl-4,13-bis[[(2S)-1-ethoxy-1-oxo-3-phenylpropan-2-yl]amino]-4,13-dioxo-6,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
prodrug
diethyl (2S,15S)-8-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-2,15-dibenzyl-4,13-bis[[(2S)-1-ethoxy-1-oxo-3-phenylpropan-2-yl]amino]-4,13-dioxo-6,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
prodrug
diethyl (2S,15S)-8-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-2,15-dibenzyl-4,13-bis[[(2S)-1-ethoxy-1-oxo-3-phenylpropan-2-yl]amino]-4,13-dioxo-7,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
prodrug
diethyl (2S,15S)-8-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-4,13-bis[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-4,13-dioxo-2,15-bis(2-phenylethyl)-6,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
-
diethyl (2S,15S)-8-[(2-amino-8-bromo-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-2,15-dibenzyl-4,13-bis[[(2S)-1-ethoxy-1-oxo-3-phenylpropan-2-yl]amino]-4,13-dioxo-7,10-dioxa-3,14-diaza-4lambda5,13lambda5-diphosphahexadecane-1,16-dioate
prodrug
guanine ribose 5'-phosphate
-
-
Hg2+
-
complete inhibition at 3 mM after 3 min at 0°C
hypoxanthine ribose 5'-phosphate
-
-
propan-2-yl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
-
triethyl-2-phosphonobutyrate
-
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid
-
[(3S)-4-hydroxy-3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]butyl]phosphonic acid
-
competitive. 592fold lower affinity for human enzyme
[3-(guanine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methylphosphonic acid
-
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine
-
[[2-[(6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]propane-1,3-diyl]bis(oxymethylene)]bis(phosphonic acid)
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
is toxic to cells and arrests cell growth
9-[2-(phosphonomethoxy)ethyl]guanine
-
-
9-[2-(phosphonomethoxy)ethyl]guanine
-
is toxic to cells and arrests cell growth
additional information
-
no inhibition by EGTA
-
additional information
design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics, rational structure-based methods, overview
-
additional information
design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics, rational structure-based methods, overview
-
additional information
-
design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics, rational structure-based methods, overview
-
additional information
spectrometric enzyme-inhibitor binding analysis, molecular docking and molecular dynamics studies, computational binding affinity analysis, binding mode and kinetics, overview. Iso-mukaadial acetate and ursolic acid acetate ligands are docked into the binding sites of Plasmodium falciparum and human hypoxanthine-guanine phosphoribosyl transferases protein using the glide docking module, binding structure comparisons
-
additional information
synthesis and evaluation of asymmetric acyclic nucleoside bisphosphonates as inhibitors of Plasmodium falciparum hypoxanthine-guanine-(xanthine) phosphoribosyltransferase. Low Ki values are achieved by inserting an extra carbon atom in the linker connecting the N9 atom of guanine to one of the phosphonate groups
-
additional information
-
synthesis and evaluation of asymmetric acyclic nucleoside bisphosphonates as inhibitors of Plasmodium falciparum hypoxanthine-guanine-(xanthine) phosphoribosyltransferase. Low Ki values are achieved by inserting an extra carbon atom in the linker connecting the N9 atom of guanine to one of the phosphonate groups
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.053 - 1.548
5-phospho-alpha-D-ribose 1-diphosphate
0.0039 - 0.0042
diphosphate
0.0018 - 0.0075
hypoxanthine
0.025 - 3.668
5-phospho-alpha-D-ribose 1-diphosphate
0.0117
allopurinol
-
recombinant enzyme
0.0009 - 0.06
hypoxanthine
additional information
additional information
-
-
-
0.053
5-phospho-alpha-D-ribose 1-diphosphate
IMP-activated enzyme, at pH 7.4 and 23°C
0.094
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with xanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.183
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with hypoxanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.256
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with hypoxanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.263
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with guanine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.275
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with guanine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.277
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with xanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.546
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 28°C, recombinant chimeric mutant enzyme with substrate hypoxanthine
0.972
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with hypoxanthine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
1.075
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 28°C, recombinant chimeric mutant enzyme, with substrate guanine
1.08
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, at pH 7.4 and 23°C
1.084
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with xanthine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
1.548
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with guanine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.0039
diphosphate
unactivated enzyme, at pH 7.4 and 23°C
0.0042
diphosphate
IMP-activated enzyme, at pH 7.4 and 23°C
0.0011
guanine
pH 7.4, 28°C, recombinant chimeric mutant enzyme
0.002
guanine
unactivated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.0025
guanine
activated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.0048
guanine
unactivated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.0018
hypoxanthine
pH 7.4, 28°C, recombinant chimeric mutant enzyme
0.005
hypoxanthine
unactivated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.005
hypoxanthine
unactivated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.0075
hypoxanthine
activated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.0016
IMP
unactivated enzyme, at pH 7.4 and 23°C
0.007
IMP
IMP-activated enzyme, at pH 7.4 and 23°C
0.036
xanthine
activated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.045
xanthine
unactivated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.078
xanthine
unactivated enzyme, at pH 7.4 and 23°C
0.078
xanthine
unactivated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.101
xanthine
IMP-activated enzyme, at pH 7.4 and 23°C
0.332
xanthine
pH 7.4, 28°C, recombinant chimeric mutant enzyme
0.025
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme
0.03
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22°C, recombinant wild-type enzyme, with hypoxanthine
0.079
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22°C, recombinant wild-type enzyme, with xanthine
0.094
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated mutant W181Y
0.102
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22°C, recombinant mutant L44F, with hypoxanthine
0.116
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22°C, recombinant mutant L44F, with guanine
0.151
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22°C, recombinant mutant L44F, with xanthine
0.201
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22°C, recombinant wild-type enzyme, with guanine
0.233
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated mutant W181F
0.251
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated mutant W181S
1.084
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated wild-type enzyme
2.286
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated mutant W181S
2.783
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated mutant W181Y
3.668
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated mutant W181F
0.001
guanine
-
pH 7.4, 22°C, recombinant wild-type enzyme
0.0011
guanine
-
recombinant chimeric mutant DS1
0.0014
guanine
-
recombinant enzyme, with other purine
0.002
guanine
-
pH 7.4, 22°C, recombinant mutant L44F
0.362
guanine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate
0.0009
hypoxanthine
-
recombinant enzyme, with other purine
0.001
hypoxanthine
-
pH 7.4, 22°C, recombinant wild-type enzyme and mutant L44F
0.0014
hypoxanthine
-
recombinant chimeric mutant DS1
0.06
hypoxanthine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate
0.17
xanthine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate, pH 8.5
0.261
xanthine
-
pH 7.4, 22°C, recombinant wild-type enzyme
0.3
xanthine
-
above, purified recombinant chimeric enzyme DS1
0.42
xanthine
-
recombinant enzyme, pH 8.5
0.853
xanthine
-
pH 7.4, 22°C, recombinant mutant L44F
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.04 - 1.6
5-phospho-alpha-D-ribose 1-diphosphate
0.1 - 1.6
5-phospho-alpha-D-ribose 1-diphosphate
0.073 - 1.13
hypoxanthine
0.04
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with guanine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.1
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with guanine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.1
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with hypoxanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.2
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with hypoxanthine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.2
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, at pH 7.4 and 23°C
0.2
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with hypoxanthine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.2
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with xanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.2
5-phospho-alpha-D-ribose 1-diphosphate
unactivated enzyme, with xanthine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.3
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with hypoxanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.4
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with guanine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.4
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with guanine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
1
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with xanthine as cosubstrate, in 10 mM potassium phosphate, at pH 7.4 and 23°C
1.6
5-phospho-alpha-D-ribose 1-diphosphate
activated enzyme, with xanthine as cosubstrate, in 100 mM Tris-HCl, at pH 7.4 and 23°C
1.6
5-phospho-alpha-D-ribose 1-diphosphate
IMP-activated enzyme, at pH 7.4 and 23°C
0.06
guanine
unactivated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.1
guanine
unactivated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.3
guanine
activated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.37
guanine
pH 7.4, 28°C, recombinant chimeric mutant enzyme
0.4
guanine
activated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
25.5
guanine
pH 7.4, 28°C, wild-type enzyme
0.1
hypoxanthine
unactivated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.2
hypoxanthine
unactivated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.3
hypoxanthine
activated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.3
hypoxanthine
activated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.47
hypoxanthine
pH 7.4, 28°C, recombinant chimeric mutant enzyme
7.1
hypoxanthine
pH 7.4, 28°C, wild-type enzyme
0.0036
IMP
unactivated enzyme, at pH 7.4 and 23°C
0.0042
IMP
IMP-activated enzyme, at pH 7.4 and 23°C
0.08
xanthine
pH 7.4, 28°C, recombinant chimeric mutant enzyme
0.2
xanthine
unactivated enzyme, at pH 7.4 and 23°C
0.2
xanthine
unactivated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
0.3
xanthine
unactivated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
0.8
xanthine
activated enzyme, in 10 mM potassium phosphate, at pH 7.4 and 23°C
1
xanthine
activated enzyme, in 100 mM Tris-HCl, at pH 7.4 and 23°C
1.6
xanthine
IMP-activated enzyme, at pH 7.4 and 23°C
0.1
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated mutant W181F
0.1
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated mutant W181Y
0.2
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated mutant W181F
0.2
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated wild-type enzyme
0.32
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant nonactivated mutant W181S
0.5
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated mutant W181Y
0.67
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated mutant W181S
1.6
5-phospho-alpha-D-ribose 1-diphosphate
pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme
0.013
guanine
-
purified recombinant chimeric enzyme DS1
1.1
guanine
-
pH 7.4, 22°C, recombinant mutant L44F
1.2
guanine
-
pH 7.4, 22°C, recombinant wild-type enzyme
0.073
hypoxanthine
-
purified recombinant chimeric enzyme DS1
0.94
hypoxanthine
-
pH 7.4, 22°C, recombinant mutant L44F
1.13
hypoxanthine
-
pH 7.4, 22°C, recombinant wild-type enzyme
0.062
xanthine
-
purified recombinant chimeric enzyme DS1
1.2
xanthine
-
pH 7.4, 22°C, recombinant mutant L44F
2.9
xanthine
-
pH 7.4, 22°C, recombinant wild-type enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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0.00049
(3-hydroxy-2-[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]methyl]propyl)phosphonic acid
at pH 7.6 and 37°C
0.0000276
3-((7-hydroxy-1H-pyrazolo[4,3-d]pyrimidin-3-yl)methylamino)propylphosphonate
at pH 7.6 and 37°C
0.000019
[(+/-)-2(R/S)-3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propoxy]phosphonic acid
at pH 7.6 and 37°C
0.0094
[(+/-)-2(R/S)-[([2-chloro-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
at pH 7.6 and 37°C
0.0000143
[(2R)-2-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
at pH 7.6 and 37°C
0.0000024
[(2R)-3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propoxy]phosphonic acid
at pH 7.6 and 37°C
0.00065
[(2S)-2-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
at pH 7.6 and 37°C
0.00098
[(2S,3R)-2,4-dihydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butoxy]phosphonic acid
at pH 7.6 and 37°C
0.0000012 - 0.0000234
[(3R)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
0.000087
[(3S)-1,1-difluoro-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
at pH 7.6 and 37°C
0.0001
[(3S)-3-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-1,1-difluoro-4-hydroxybutyl]phosphonic acid
at pH 7.6 and 37°C
0.00000065
[(3S)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
at pH 7.6 and 37°C
0.0000091
[2-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propyl] phosphonic acid
at pH 7.6 and 37°C
0.00062
[2-[(2-[4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]ethyl)amino]ethyl]phosphonic acid
at pH 7.6 and 37°C
0.0144
[2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]ethoxy]phosphonic acid
at pH 7.6 and 37°C
0.0153
[3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-2-(hydroxymethyl)propoxy]phosphonic acid
at pH 7.6 and 37°C
0.02
[3-[(2-[4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]ethyl)amino]propyl]phosphonic acid
at pH 7.6 and 37°C
0.00049
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
at pH 7.6 and 37°C
0.0019
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]ethyl]phosphonic acid
at pH 7.6 and 37°C
0.02
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]methyl]phosphonic acid
at pH 7.6 and 37°C
0.0086
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]pentyl]phosphonic acid
at pH 7.6 and 37°C
0.0000106
[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propyl]phosphonic acid
at pH 7.6 and 37°C
0.00001 - 0.00006
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid
0.000014 - 0.00008
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid
0.00001
(3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]propyl)phosphonic acid
-
pH 7.6, 37°C
0.02
(R)-9-[2-(phosphonomethoxy)propyl]-8-bromoguanine
-
pH 7.4, 25°C
0.4373
(R)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
pH 8.5, 25°C
0.0006
(R,S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25°C
0.0004 - 0.0026
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid
0.045
(S)-9-[2-(phosphonomethoxy)propyl]-8-azaguanine
-
above, pH 7.4, 25°C
0.011
(S)-9-[2-(phosphonomethoxy)propyl]-8-bromoguanine
-
pH 7.4, 25°C
0.0648
(S)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
pH 8.5, 25°C
0.0284
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25°C
0.5
6-methylheptyl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
above, pH 7.4, 25°C
0.0001
9-[2-(2-phosphonoethoxy)ethyl]guanine
-
pH 7.4, 25°C
0.0003
9-[2-(2-phosphonoethoxy)ethyl]hypoxanthine
-
pH 7.4, 25°C
0.0036
9-[2-(phosphonomethoxy)-3-fluoro-propyl]guanine
-
pH 8.5, 25°C
0.1
9-[2-(phosphonomethoxy)ethyl]-6-thioguanine
-
above, pH 7.4, 25°C
0.0072
9-[2-(phosphonomethoxy)ethyl]-7-deaza-8-azahypoxanthine
-
pH 7.4, 25°C
0.003
9-[2-(phosphonomethoxy)ethyl]-8-azaguanine
-
pH 7.4, 25°C
0.01
9-[2-(phosphonomethoxy)ethyl]-8-bromoguanine
-
pH 7.4, 25°C
0.0016 - 0.0189
9-[2-(phosphonomethoxy)ethyl]guanine
0.0012
9-[2-(phosphonomethoxy)ethy]-8-hydroxyguanine
-
pH 7.4, 25°C
0.001 - 0.0014
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
0.008 - 0.0377
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
0.01
guanine ribose 5'-phosphate
-
pH 7.4, 25°C
0.0036
hypoxanthine ribose 5'-phosphate
-
pH 7.4, 25°C
0.2
propan-2-yl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
above, pH 7.4, 25°C
0.000002 - 0.000006
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid
0.00000065
[(3S)-4-hydroxy-3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]butyl]phosphonic acid
-
pH 7.6, 37°C
0.000006
[3-(guanine-9-yl)-2-((2-phosphonoethoxy)methyl)propoxy]methylphosphonic acid
pH 7.4, temperature not specified in the publication
0.000007 - 0.000008
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine
0.0000012
[(3R)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
at pH 7.6 and 37°C
0.0000234
[(3R)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
at pH 7.6 and 37°C
0.00001
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid
pH not specified in the publication, 37°C
0.00006
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid
pH not specified in the publication, 37°C
0.000014
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid
pH not specified in the publication, 37°C
0.00008
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid
pH not specified in the publication, 37°C
0.0004
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid
pH not specified in the publication, 37°C
0.0026
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid
pH not specified in the publication, 37°C
0.0016
9-[2-(phosphonomethoxy)ethyl]guanine
-
pH 7.4, 25°C
0.0189
9-[2-(phosphonomethoxy)ethyl]guanine
-
pH 8.5, 25°C
0.001
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25°C
0.0014
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25°C
0.008
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25°C
0.0377
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25°C
0.000002
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid
pH not specified in the publication, 37°C
0.000006
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid
pH not specified in the publication, 37°C
0.000007
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine
pH not specified in the publication, 37°C
0.000008
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine
pH not specified in the publication, 37°C
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F197W
the mutant shows reduced activity compared tot he wild type enzyme
W181S/F197W
the mutant shows reduced activity compared tot he wild type enzyme
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)
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)
L44F
-
site-directed mutagenesis, mutant does not phosphoribosylate guanine and xanthine, modulation via loop IV influence the substrate specificity, altered enzyme stability
L44F
-
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
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
-
construction of 4 chimeric enzymes with segments of human and Plasmodium falciparum enzymes, altered substrate specificities
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
-
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
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Keough, D.T.; Ng, A.L.; Winzor, D.J.; Emmerson, B.T.; de Jersey, J.
Purification and characterization of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase and comparison with the human enzyme
Mol. Biochem. Parasitol.
98
29-41
1999
Homo sapiens, Plasmodium falciparum
brenda
Sujay Subbayya, I.N.; Sukumaran, S.; Shivashankar, K.; Balaram, H.
Unusual substrate specificity of a chimeric hypoxanthine-guanine phosphoribosyltransferase containing segments from the Plasmodium falciparum and human enzymes
Biochem. Biophys. Res. Commun.
272
596-602
2000
Homo sapiens, Plasmodium falciparum
brenda
Raman, J.; Sumathy, K.; Anand, R.P.; Balaram, H.
A non-active site mutation in human hypoxanthine guanine phosphoribosyltransferase expands substrate specificity
Arch. Biochem. Biophys.
427
116-122
2004
Plasmodium falciparum, Homo sapiens (P00492), Homo sapiens
brenda
Raman, J.; Ashok, C.S.; Subbayya, S.I.; Anand, R.P.; Selvi, S.T.; Balaram, H.
Plasmodium falciparum hypoxanthine guanine phosphoribosyltransferase. Stability studies on the product-activated enzyme
FEBS J.
272
1900-1911
2005
Plasmodium falciparum
brenda
Mbewe, B.; Chibale, K.; McIntosh, D.B.
Purification of human malaria parasite hypoxanthine guanine xanthine phosphoribosyltransferase (HGXPRT) using immobilized Reactive Red 120
Protein Expr. Purif.
52
153-158
2007
Plasmodium falciparum
brenda
Keough, D.T.; Hockova, D.; Holy, A.; Naesens, L.M.; Skinner-Adams, T.S.; Jersey, J.; Guddat, L.W.
Inhibition of hypoxanthine-guanine phosphoribosyltransferase by acyclic nucleoside phosphonates: a new class of antimalarial therapeutics
J. Med. Chem.
52
4391-4399
2009
Plasmodium falciparum, Homo sapiens (P00492), Homo sapiens
brenda
Gayathri, P.; Sujay Subbayya, I.; Ashok, C.; Senthamizh Selvi, T.; Balaram, H.; Murthy, M.
Crystal structure of a chimera of human and Plasmodium falciparum hypoxanthine guanine phosphoribosyltransferases provides insights into oligomerization
Proteins
73
1010-1020
2008
Homo sapiens (P00492), Homo sapiens, Plasmodium falciparum (P20035), Plasmodium falciparum
brenda
Gogia, S.; Balaram, H.; Puranik, M.
Hypoxanthine guanine phosphoribosyltransferase distorts the purine ring of nucleotide substrates and perturbs the pKa of bound xanthosine monophosphate
Biochemistry
50
4184-4193
2011
Plasmodium falciparum, Homo sapiens (P00492), Homo sapiens
brenda
Hazleton, K.Z.; Ho, M.C.; Cassera, M.B.; Clinch, K.; Crump, D.R.; Rosario, I.; Merino, E.F.; Almo, S.C.; Tyler, P.C.; Schramm, V.L.
Acyclic immucillin phosphonates: second-generation inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
Chem. Biol.
19
721-730
2012
Plasmodium falciparum
brenda
Clinch, K.; Crump, D.R.; Evans, G.B.; Hazleton, K.Z.; Mason, J.M.; Schramm, V.L.; Tyler, P.C.
Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
Bioorg. Med. Chem.
21
5629-5646
2013
Homo sapiens, Plasmodium falciparum (P20035)
brenda
Karnawat, V.; Gogia, S.; Balaram, H.; Puranik, M.
Differential distortion of purine substrates by human and Plasmodium falciparum hypoxanthine-guanine phosphoribosyltransferase to catalyse the formation of mononucleotides
ChemPhysChem
16
2172-2181
2015
Homo sapiens (P00492), Homo sapiens, Plasmodium falciparum (P20035), Plasmodium falciparum
brenda
Roy, S.; Nagappa, L.K.; Prahladarao, V.S.; Balaram, H.
Kinetic mechanism of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
Mol. Biochem. Parasitol.
204
111-120
2015
Plasmodium falciparum (P20035), Plasmodium falciparum
brenda
Roy, S.; Karmakar, T.; Prahlada Rao, V.S.; Nagappa, L.K.; Balasubramanian, S.; Balaram, H.
Slow ligand-induced conformational switch increases the catalytic rate in Plasmodium falciparum hypoxanthine guanine xanthine phosphoribosyltransferase
Mol. Biosyst.
11
1410-1424
2015
Plasmodium falciparum (P20035), Plasmodium falciparum
brenda
Keough, D.T.; Rejman, D.; Pohl, R.; Zbornikova, E.; Hockova, D.; Croll, T.; Edstein, M.D.; Birrell, G.W.; Chavchich, M.; Naesens, L.M.J.; Pierens, G.K.; Brereton, I.M.; Guddat, L.W.
Design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics
ACS Chem. Biol.
13
82-90
2018
Plasmodium falciparum (A0A1G4HBT9), Plasmodium falciparum (Q8IJS1), Plasmodium falciparum, Homo sapiens (P00492)
brenda
Ducati, R.G.; Firestone, R.S.; Schramm, V.L.
Kinetic isotope effects and transition state structure for hypoxanthine-guanine-xanthine phosphoribosyltransferase from Plasmodium falciparum
Biochemistry
56
6368-6376
2017
Plasmodium falciparum (Q8IJS1)
brenda
Opoku, F.; Govender, P.P.; Pooe, O.J.; Simelane, M.B.C.
Evaluating iso-mukaadial acetate and ursolic acid acetate as Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase inhibitors
Biomolecules
9
861
2019
Plasmodium falciparum (Q8IJS1)
brenda
Spacek, P.; Keough, D.T.; Chavchich, M.; Dracinsky, M.; Janeba, Z.; Naesens, L.; Edstein, M.D.; Guddat, L.W.; Hockova, D.
Synthesis and evaluation of asymmetric acyclic nucleoside bisphosphonates as inhibitors of Plasmodium falciparum and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferase
J. Med. Chem.
60
7539-7554
2017
Homo sapiens (P00492), Homo sapiens, Plasmodium falciparum (Q8IJS1), Plasmodium falciparum
brenda
Roy, S.; Karmakar, T.; Nagappa, L.K.; Prahlada Rao, V.S.; Balasubramanian, S.; Balaram, H.
Role of W181 in modulating kinetic properties of Plasmodium falciparum hypoxanthine guanine xanthine phosphoribosyltransferase
Proteins
84
1658-1669
2016
Plasmodium falciparum (Q8IJS1), Plasmodium falciparum
brenda