Acyclic phosphonate nucleotides and human adenylate kinases: impact of a borano group on alpha-P position.
Adenylate kinases are involved in the activation of antiviral drugs such as the acyclic phosphonates analogs PMEA and (R)PMPA. We examine the in vitro phosphorylation of PMEA and PMPA bearing a borano- or a H- group on the phosphorus atom. The alpha-borano or alpha-H on PMEA and PMPA were detrimental to the activity of recombinant human AMP kinases 1 and 2. Docking PMEA to the active site of AMP kinase 1 indicated that the borano group may prevent two conserved critical Arg interactions with the alpha-phosphate, resulting in substrate bad positioning.
Topalis
D
D
Laboratoire d'Enzymologie, Université Paris, Paris, France.
Alvarez
K
K
Barral
K
K
Munier-Lehmann
H
H
Schneider
B
B
Véron
M
M
Guerreiro
C
C
Mulard
L
L
El-Amri
C
C
Canard
B
B
Deville-Bonne
D
D
D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001665:Binding Sites; D001880:Boranes / Q000378:metabolism*; D020134:Catalytic Domain; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D009711:Nucleotides / Q000378:metabolism*; D063065:Organophosphonates / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000068698:Tenofovir
D001880:Boranes; D007527:Isoenzymes; D009711:Nucleotides; D063065:Organophosphonates; D011994:Recombinant Proteins; C053001:adefovir; D000255:Adenosine Triphosphate; D000068698:Tenofovir; D000263:Adenylate Kinase; C110939:adenylate kinase 1; C110938:adenylate kinase 2; D000225:Adenine