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Literature summary for 2.5.1.15 extracted from

  • Yogavel, M.; Nettleship, J.E.; Sharma, A.; Harlos, K.; Jamwal, A.; Chaturvedi, R.; Sharma, M.; Jain, V.; Chhibber-Goel, J.; Sharma, A.
    Structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase-dihydropteroate synthase from Plasmodium vivax sheds light on drug resistance (2018), J. Biol. Chem., 293, 14962-14972 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.5.1.15

Cloned(Commentary)

Cloned (Comment) Organism
-
 Plasmodium vivax
expressed in Escherichia coli Rosetta pLysS cells Plasmodium vivax

Crystallization (Commentary)

Crystallization (Comment) Organism
hanging-drop vapor-diffusion method at 20°C, crystal structure of the enzyme in complex with four substrates/analogs Plasmodium vivax
in complex with 6-hydroxymethylpterin diphosphate, pterin, the ATP analog AMPCPP, and 4-aminobenzoate, at 20°C, hanging drop vapor diffusion method, using 20% (w/v) PEG 3350, 0.2 M potassium citrate tribasic monohydrate Plasmodium vivax
structure of HPPk-DHPS in complex with four substrates/analogs. Plasmodium vivax

Protein Variants

Protein Variants Comment Organism
A383G drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
A383G the mutation confers resistance to sulfadoxine Plasmodium vivax
A383G dominant drug resistance mutation. Mutation subtly alters the intricate enzyme-4-amino benzoic acid-sulfadoxine interactions such that DHPS affinity for 4-amino benzoic acid is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
A553G drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
A553G the mutation confers resistance to sulfadoxine Plasmodium vivax
A553G dominant drug resistance mutation. Mutation subtly alters the intricate enzyme-4-amino benzoic acid-sulfadoxine interactions such that DHPS affinity for 4-amino benzoic acid is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
K512D drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
K512D the mutation confers resistance to sulfadoxine Plasmodium vivax
K512D dominant drug resistance mutation. Mutation subtly alters the intricate enzyme-4-amino benzoic acid-sulfadoxine interactions such that DHPS affinity for 4-amino benzoic acid is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
K512E drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
K512E the mutation confers resistance to sulfadoxine Plasmodium vivax
K512E dominant drug resistance mutation. Mutation subtly alters the intricate enzyme-4-amino benzoic acid-sulfadoxine interactions such that DHPS affinity for 4-amino benzoic acid is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
S382A drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
S382A the mutation confers resistance to sulfadoxine Plasmodium vivax
S382A dominant drug resistance mutation. Mutation subtly alters the intricate enzyme-4-amino benzoic acid-sulfadoxine interactions such that DHPS affinity for 4-amino benzoic acid is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
V585A drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax
V585A the mutation confers resistance to sulfadoxine Plasmodium vivax
V585A dominant drug resistance mutation. Mutation subtly alters the intricate enzyme-4-amino benzoic acid-sulfadoxine interactions such that DHPS affinity for 4-amino benzoic acid is diminished only moderately, but its affinity for sulfadoxine is changed substantially Plasmodium vivax

Inhibitors

Inhibitors Comment Organism Structure
sulfadoxine
-
 Plasmodium vivax

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate Plasmodium vivax
-
 diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate Plasmodium vivax Salvador 1
-
 diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate Plasmodium vivax Salvador I
-
 diphosphate + 7,8-dihydropteroate
-
 ?
6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate Plasmodium vivax
-
 diphosphate + 7,8-dihydropteroate
-
 ?

Organism

Organism UniProt Comment Textmining
Plasmodium vivax
-
-
-
Plasmodium vivax A5JZS1
-
-
Plasmodium vivax A5JZS1 bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and dihydropteroate synthase, cf. EC 2.7.6.3
-
Plasmodium vivax Salvador I A5JZS1
-
-
Plasmodium vivax Salvador I A5JZS1 bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and dihydropteroate synthase, cf. EC 2.7.6.3
-

Purification (Commentary)

Purification (Comment) Organism
Ni-NTA agarose column chromatography, Q-Sepharose column chromatography, phenyl FF 16/10 column chromatography, and Superdex S-200 gel filtration Plasmodium vivax

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate
-
 Plasmodium vivax diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate
-
 Plasmodium vivax Salvador 1 diphosphate + 7,8-dihydropteroate
-
 ?
(7,8-dihydropterin-6-yl)methyl diphosphate + 4-aminobenzoate
-
 Plasmodium vivax Salvador I diphosphate + 7,8-dihydropteroate
-
 ?
6-hydroxymethyl-7,8-dihydropterin diphosphate + 4-aminobenzoate
-
 Plasmodium vivax diphosphate + 7,8-dihydropteroate
-
 ?

Synonyms

Synonyms Comment Organism
6-hydroxymethyl-7,8-dihydropterin-pyrophosphokinase-dihydropteroate synthase bifunctional enzyme Plasmodium vivax
HPPK-DHPS
-
 Plasmodium vivax
HPPK-DHPS bifunctional enzyme with 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase and dihydropteroate synthase activities Plasmodium vivax
PvHPPK-DHPS
-
 Plasmodium vivax
PVX_123230
-
 Plasmodium vivax

General Information

General Information Comment Organism
drug target the enzyme is target of drugs like sulfadoxine (SDX). The SDX effectiveness as an antimalarial drug is increasingly diminished by the rise and spread of drug-resistant mutations Plasmodium vivax
metabolism reactions in the folate biosynthetic pathway Plasmodium vivax