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Polyamine binding
About: Polyamine binding is a research topic. Over the lifetime, 188 publications have been published within this topic receiving 9206 citations.
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TL;DR: Spermidine, when crosslinked with dimethyl suberimidate, bound to S2, S14, S20, L4, L5, L9, L13, and L16 proteins, and the relationship between the binding site(s) of polyamine on ribosomes and the function of polyamines is discussed.
21 citations
TL;DR: Polyamine binding sites have been localized in ram spermatozoa using biochemical and cytochemical tools and the role of spermine in the acrosome reaction and Ca2+ fluxes in sperm cells is discussed.
21 citations
TL;DR: The data demonstrate that gene-specific polyamine removal is a major transcriptional regulatory mechanism active in high-grade gliomas that drives poor outcomes.
Abstract: Spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme in polyamine catabolism, has broad regulatory roles due to near ubiquitous polyamine binding. We describe a novel function of SAT1 as a gene-specific transcriptional regulator through local polyamine acetylation. SAT1 expression is elevated in aggressive brain tumors and promotes resistance to radiotherapy. Expression profiling in glioma cells identified SAT1 target genes that distinguish high- and low-grade tumors, in support of the prognostic utility of SAT1 expression. We further discovered mechanisms of SAT1-driven tumor aggressiveness through promotion of expression of both DNA damage response pathways as well as cell cycle regulatory genes. Mechanistically, SAT1 associates specifically with the promoter of the MELK gene, which functionally controls other SAT1 targets, and leads biologically to maintenance of neurosphere stemness in conjunction with FOXM1 and EZH2. CRISPR knockin mutants demonstrate the essentiality of the polyamine acetyltransferase activity of SAT1 for its function as a transcriptional regulator. Together, the data demonstrate that gene-specific polyamine removal is a major transcriptional regulatory mechanism active in high-grade gliomas that drives poor outcomes.
21 citations
TL;DR: This work develops a detailed mapping approach to localize binding sites of physiologically essential channel blockers by scanning the effects of cysteine modification at multiple pore-lining positions on the blocking properties of a library of polyamine analogs, demonstrating that the effects are position- and blocker-dependent.
20 citations
Journal Article•
TL;DR: It is suggested that spermine and spermidines could increase anesthetic potency by acting at a site on the NMDA receptor which negatively modulates the binding of MK-801, which is more closely linked to the activity of brain NMDA receptors than is that of pentobarbital or diethyl ether.
Abstract: Anesthetic potency was examined in mice after pretreatment with various putative agonists and antagonists of the polyamine site of the N-methyl-D-aspartate (NMDA) receptor. Anesthetic potency was determined for ethanol and pentobarbital by measurement of duration of loss of righting reflex, and for the volatile anesthetics, halothane and diethyl ether, by measurement of the minimum alveolar concentration (MAC). The polyamines, spermine and spermidine, increased the duration of ethanol and pentobarbital anesthesia and reduced halothane MAC, but had no effect on diethyl ether MAC. Putative antagonists of the polyamine site, ifenprodil and arcaine, also increased the anesthetic potency of ethanol, but diaminodecane, an inverse agonist, was inactive. Concurrent pretreatment with spermine or ifenprodil reduced the ability of MK-801 to increase ethanol anesthesia duration, but did not alter the ability of CGS 19755 to increase ethanol anesthesia duration. Although this study did not rule out effects of polyamines on other neurochemical systems, these results suggest that spermine and spermidines could increase anesthetic potency by acting at a site on the NMDA receptor which negatively modulates the binding of MK-801. Results of this study also suggest that the anesthetic potency of ethanol and halothane is more closely linked to the activity of brain NMDA receptors than is that of pentobarbital or diethyl ether.
20 citations