Disease relevance of beta-Hydroxynorvaline

• Inhibition of synthesis of herpesvirus (HSV-1) glycoproteins and endogenous fusion by beta-hydroxynorvaline in BHK-21 cells [1].

High impact information on beta-Hydroxynorvaline

• We have shown previously that processing of preprolactin to prolactin in isolated rat pituitaries is inhibited by the threonine analog, beta-hydroxynorvaline (Hnv), presumably because of its substitution for the threonine at the cleavage site [2].
• Incorporation of the threonine analogue beta-hydroxynorvaline produced species approximately 2.5 kDa and approximately 5 kDa smaller than the fully glycosylated pro-MPO, suggesting that two of the glycans were in the asparagine-X-threonine tripeptide sequence [3].
• Both the capacity to undergo autolytic cleavage and the Mr increase were inhibited by cell culture in the presence of the antibiotic tunicamycin or the threonine analog beta-hydroxynorvaline, both of which inhibit glycosylation [4].
• The amino acid side chain was characterized as 3-hydroxynorvaline (3) by gas chromatography-mass spectrometry of the trimethylsilyl derivative after cleavage from 1 and 2 by alkaline hydrolysis [5].
• Treatment of HSV-infected cells with 5-10 mM beta-hydroxynorvaline (Hnv), a threonine analog, specifically affects herpesvirus DNA replication: both the rate of and total DNA synthesis are reduced, the former approximately 15-fold by Hnv (6 h post-infection) and the latter by 12-fold (between 3 and 12 h post-infection) [6].

Biological context of beta-Hydroxynorvaline

• It is suggested that beta-hydroxynorvaline is incorporated into these enzyme(s), either close to or at the active site thus perturbing viral DNA synthesis. beta-Hydroxynorvaline should have unique utility as a targeted antiviral compound, acting on both membrane-mediated phenomena (fusion, penetration and attachment) and DNA replication [6].

Anatomical context of beta-Hydroxynorvaline

• These data suggest that the absence of carbohydrate side chains in cathepsin D results in an enhancement of the degradation rate of the precursor in the endoplasmic reticulum, and the replacement of threonine by beta-hydroxynorvaline in an enhanced degradation of the mature cathepsin D in lysosomes [7].

Gene context of beta-Hydroxynorvaline

• Inhibition of herpesvirus-induced thymidine kinase and DNA polymerase by beta-hydroxynorvaline [6].
• Treatment of HSV-infected BHK-21 cells with 5-10 mM of beta-hydroxynorvaline (Hnv), an analog of threonine which blocked attachment of oligosaccharides at the Asn-X-Thr sites, markedly inhibited the synthesis of all viral glycoproteins as well as the major capsid protein [1].

References