PMID- 23979753 OWN - NLM STAT- MEDLINE DCOM- 20140514 LR - 20211021 IS - 1098-6596 (Electronic) IS - 0066-4804 (Print) IS - 0066-4804 (Linking) VI - 57 IP - 11 DP - 2013 Nov TI - Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates. PG - 5760-2 LID - 10.1128/AAC.00978-13 [doi] AB - Dihydroxymethyl and monohydroxymethyl methylenecyclopropane nucleosides are effective inhibitors of both variants of human herpesvirus 6 (HHV-6). We investigated involvement of HHV-6 U69 protein kinase in their mechanism of action. Phosphorylation of the dihydroxymethyl analogue cyclopropavir and monohydroxymethyl nucleosides with either a 6-ether moiety (MBX 2168) or a 6-thioether moiety (MBX 1616) with purified U69 was examined. All three compounds were substrates of this viral kinase and had similar Michaelis-Menten kinetic parameters. FAU - Komazin-Meredith, Gloria AU - Komazin-Meredith G AD - Microbiotix, Inc., Worcester, Massachusetts, USA. FAU - Cardinale, Steven C AU - Cardinale SC FAU - Williams, John D AU - Williams JD FAU - Peet, Norton P AU - Peet NP FAU - Prichard, Mark N AU - Prichard MN FAU - Bowlin, Terry L AU - Bowlin TL LA - eng GR - R43 AI082799/AI/NIAID NIH HHS/United States GR - R44 AI082799/AI/NIAID NIH HHS/United States GR - R44 AI 082799/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130826 PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Antiviral Agents) RN - 0 (Cyclopropanes) RN - 0 (Nucleosides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Viral Proteins) RN - 5Z93L87A1R (Guanine) RN - EAO0TD9B13 (cyclopropavir) RN - EC 2.7.- (Protein Kinases) SB - IM MH - Antiviral Agents/*chemistry MH - Baculoviridae/genetics MH - Cyclopropanes/*chemistry MH - Enzyme Assays MH - Guanine/*analogs & derivatives/chemistry MH - Herpesvirus 6, Human/chemistry/*enzymology MH - Humans MH - Kinetics MH - Nucleosides/*chemistry MH - Phosphorylation MH - Protein Kinases/*chemistry/genetics/isolation & purification MH - Recombinant Fusion Proteins/chemistry/genetics/isolation & purification MH - Substrate Specificity MH - Viral Proteins/*chemistry/genetics/isolation & purification PMC - PMC3811273 EDAT- 2013/08/28 06:00 MHDA- 2014/05/16 06:00 PMCR- 2014/05/01 CRDT- 2013/08/28 06:00 PHST- 2013/08/28 06:00 [entrez] PHST- 2013/08/28 06:00 [pubmed] PHST- 2014/05/16 06:00 [medline] PHST- 2014/05/01 00:00 [pmc-release] AID - AAC.00978-13 [pii] AID - 00978-13 [pii] AID - 10.1128/AAC.00978-13 [doi] PST - ppublish SO - Antimicrob Agents Chemother. 2013 Nov;57(11):5760-2. doi: 10.1128/AAC.00978-13. Epub 2013 Aug 26.