Adenylylsulfate–ammonia adenylyltransferase activity is another inherent property of Fhit proteins

Abstract

SynopsisFhits (fragile histidine triad proteins) occur in eukaryotes but their function is largely unknown, although human Fhit is believed to act as a tumour suppressor. Fhits also exhibit dinucleoside triphosphatase, adenylylsulfatase and nucleoside phosphoramidase activities that in each case yield nucleoside 5 -monophosphate as a product. Due to the dinucleoside triphosphatase activity, Fhits may also be involved in mRNA decapping. In the present study, we demonstrate Fhit-catalysed ammonolysis of adenosine 5 -phosphosulfate, which results in the formation of adenosine 5 -phosphoramidate. This reaction has previously been associated with adenylylsulfate-ammonia adenylyltransferase (EC 2.7.7.51). Our finding shows that the capacity to catalyse ammonolysis is another inherent property of Fhits. Basic kinetic parameters and substrate specificity of this reaction catalysed by human Fhit are presented.

New Insight into Plant Signaling: Extracellular ATP and Uncommon Nucleotides

“…Furthermore, their food uptake and gas exchange take place through external surfaces (leaves: light and CO2, roots: ions and water). Plants must, therefore, possess systems to exchange information throughout the entire plant to ensure the coordination of plant development As described above, in plants, the presence of enzymes degrading and synthesizing another uncommon nucleotide, NH 2 -pA, has been described [127,132]. It was evidenced that NH 2 -pA regulates the expression of genes coding enzymes of the phenylpropanoid pathway, such as PAL, cinnamate-4-hydroxylase (C4H), 4CL, CHS, CCR, and isochorismate synthase (ICS) in Arabidopsis thaliana seedlings.…”

“…Similarly to p n Ns, the level of NH 2 -pA in a cell is enzymatically controlled. It is known that NH 2 -pA can be synthesized by adenylyl sulfate:ammonia adenylyltransferase (EC 2.7.7.51) in the algae Chlorella pyrenoidosa, Euglena gracilis, amoeba Dictyostelium discoideum, bacteria Escherichia coli, and in higher plants Hordeum vulgare, Spinacia oleracea [126], and Lupinus luteus [127]. This transferase catalyzes the following reaction: SO 4 -pA + NH 4 + → NH 2 -pA + SO 4 2− + 2H + .…”

“…The most common NpnN is Ap4A, which The supposition that NH 2 -pA is a ubiquitous compound and that its concentration is enzymatically controlled may be supported by the existence of various enzymes that catalyze the cleavage of NH 2 -pA to ammonia and AMP (pA) by hydrolysis [128][129][130][131][132][133], or to ammonia and ADP (ppA) by phosphorolysis [130]. Both the synthesis [127] and the degradation [131] of NH 2 -pA can be controlled by HIT (histidine triad) proteins. One of the proteins belonging to the HIT family proteins is Fhit (fragile histidine triad).…”

“…Recently it has been shown that NH 2 -pA can also be synthesized by Fhit proteins from Lupinus luteus seeds and Arabidopsis thaliana. It catalyzes the ammonolysis of SO 4 -pA, leading to the formation of NH 2 -pA [127].…”

Progress of nitrogen-phosphorus bond biosynthesis study of naturally occurring phosphoramidates

“…作为一种新的抑癌基因 [26] , 其所编码的蛋白Fhit不仅 具 有 催 化 二 腺 苷 三 磷 酸 (ApppA) 水 解 生 成 AMP 和 ADP的活性 [27] , 还具有腺苷酰基转移酶的活性. Fhit 可以催化APS和腺苷5′-氟代磷酸(F-pA)或二腺苷三 磷酸(ApppA)发生氨解反应, 产生AMP-NH 2 , 并依据 已经揭示的Fhit作用于磷手性底物的特性, 提出假 设, Fhit催化氨解反应是由NH 3 进攻Fhit-核苷酸共价 结合体 [28] , 但APS氨解的酶学机制还需经严格的实 验数据验证. [29] .…”