title: N6-methyl-AMP aminohydrolase activates N6-substituted purine acyclic nucleoside phosphonates.
abstract: In this study we present the identification and characterization of the enzyme involved in the N6-cyclopropyl-2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (N6-cyclopropyl-PMEDAP) conversion to biologically active 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) as well as abacavir 5'-phosphate to carbovir 5'-phosphate. This enzyme was purified from rat liver to homogeneity; it appears to be composed from six 42 kDa subunits and its native form has the molecular weight 260 kDa. This so far unknown enzyme catalyzes conversion of both N6-methyl-AMP and N6-methyl-dAMP to IMP and/or dIMP, respectively. The enzyme acts as 6-(N-substituted amino)purine 5'-nucleotide aminohydrolase with the reaction mechanism very similar to AMP deaminase. The enzyme does not deaminate AMP and dAMP, or the corresponding nucleosides. It is inhibited by deoxycoformycin 5'-phosphate but not by deoxycoformycin or erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA).
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic. schinkmanova@uochb.cas.cz
authors.forename: Markéta
authors.initials: M
authors.lastname: Schinkmanová
authors.forename: Ivan
authors.initials: I
authors.lastname: Votruba
authors.forename: Antonín
authors.initials: A
authors.lastname: Holý
mesh_terms: D000225:Adenine / Q000378:metabolism; D000619:Aminohydrolases / Q000302:isolation & purification* / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D063065:Organophosphonates / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C120401:N(6)-cyclopropyl-9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011355:Prodrugs; C063380:9-((2-phosphonylmethoxy)ethyl)guanine; D006147:Guanine; D000619:Aminohydrolases; D000225:Adenine