N6-methyl-AMP aminohydrolase activates N6-substituted purine acyclic nucleoside phosphonates
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
16513094
DOI
10.1016/j.bcp.2006.01.013
PII: S0006-2952(06)00065-7
Knihovny.cz E-zdroje
- MeSH
- adenin metabolismus MeSH
- aminohydrolasy izolace a purifikace metabolismus MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- guanin analogy a deriváty metabolismus MeSH
- játra enzymologie MeSH
- katalýza MeSH
- krysa rodu Rattus MeSH
- organofosfonáty metabolismus MeSH
- organofosforové sloučeniny metabolismus MeSH
- potkani Sprague-Dawley MeSH
- prekurzory léčiv metabolismus MeSH
- techniky in vitro MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 9-((2-phosphonylmethoxy)ethyl)guanine MeSH Prohlížeč
- adenin MeSH
- aminohydrolasy MeSH
- guanin MeSH
- N(6)-cyclopropyl-9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Prohlížeč
- organofosfonáty MeSH
- organofosforové sloučeniny MeSH
- prekurzory léčiv MeSH
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).
Citace poskytuje Crossref.org
Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects
