One striking feature was the current presence of PPP-family protein phosphatases for the reason that were absent in (AtSLP1 and -2 phosphatases) that demonstrated complete insensitivity to inhibition by both microcystin and okadaic acidity, with AtSLP1 exhibiting small enzymatic activation.7 Bioinformatic analysis conclusively placed the AtSLPs as more closely linked to the PPP-family phosphatases than every other microcystin or okadaic acid insensitive protein phosphatase class (i.e., PPM, PTP and Asp-based family members phosphatases). absent in metazoans, but within an array of bacteria, protozoa and fungi in charge of individual disease. The initial biochemical properties and evolutionary traditions of SLP phosphatases suggests they cannot only be potential biotechnology targets for agriculture, but may also prove to be of interest for future therapeutic drug development. and alike the protein phosphatases are comprised of four main classes: the phospho-protein CSP-B phosphatases (PPP), Mg2+-dependent phospho-protein phosphatases (PPM/PP2C), phospho-tyrosine phosphatases (PTP) and Asp-based phosphatases.3-5 Previous efforts to directly compare the protein phosphatase complement of and found many similarities, emphasizing the central and conserved nature of protein phosphatases across diverse eukaryotes.3 However, this comparison also revealed a number of differences. One striking feature was the presence of PPP-family protein phosphatases in that were absent in (AtSLP1 and -2 phosphatases) that demonstrated complete insensitivity to inhibition by both microcystin and okadaic acid, with AtSLP1 exhibiting slight enzymatic activation.7 Bioinformatic analysis conclusively placed the AtSLPs as more closely related to the PPP-family phosphatases than any other microcystin or okadaic acid insensitive protein phosphatase class (i.e., PPM, PTP and Asp-based family phosphatases). As well, within the PPP-family as a whole, the inhibitor insensitive Nifurtimox SLP phosphatases were unexpectedly found to be most related Nifurtimox to Nifurtimox the microcystin and okadaic acid sensitive PP1 and PP2A enzymes (Fig.?1B).7 Open in a separate window Figure?1. Comparison of PP1 / PP2A protein phosphatase complexes to SLP1 and 2. (A) Chemical structures of Nifurtimox PPP-family protein phosphatase inhibitors microcystin (left) and okadaic acid (right). (B) Protein phosphatase one catalytic subunits (PP1) interact with hundreds of regulatory subunits through their RVxF motif (labeled in red) to form numerous protein phosphatase complexes. Although PP1 complexes have been demonstrated to control a plethora of events in other eukaryotes, in plants to date the only defined PP1 functions are linked to cell cycle control. PP2A catalytic subunits (PP2Ac) however, interact with a select number of both regulatory B subunits (B, B and B) and scaffolding A subunits (A1, A2 and A3) to form a variety of trimeric protein phosphatases complexes. These trimeric protein complexes have been shown to regulate aspects of plant growth and metabolism. Unlike PP1 and PP2A, regulatory or scaffolding (Reg) subunits have not yet been identified for SLP protein phosphatases. The dashed line represents a currently possible, unidentified SLP interaction motif. As well, the biological role of SLP protein phosphatases has not yet been uncovered. Question marks represent events not yet resolved. SLP phosphatases identified in human pathogens In addition to an unique insensitivity to classic PPP-family protein phosphatases inhibitors, examination of SLP phosphatase phylogenetic history uncovered a complete absence of SLP phosphatases in metazoans, but a presence in a select number of bacteria, fungi and parasitic protozoa responsible for human disease.6,7,17 Two such SLP phosphatase containing protozoa are and Plasmodium, each responsible for African sleeping sickness and malaria respectively. Interestingly, these protozoa are also known to possess a vestigial plastid (chloroplast remnant) called an apicoplast as a result of their evolution from early photosynthetic, chloroplast containing eukaryotes.18,19 Moreover, both protozoa have multiple copies of SLP phosphatases, which may be reflective of different biological roles needed to accommodate the complex life cycles of these organisms. Conversely, SLP phosphatase containing bacteria and fungi were found to possess only one SLP phosphatase.6,7 Having a single SLP enzyme appears to parallel a lack of a plastid or vestigial plastid and may account for an evolutionary history that determines whether an organism has one vs. two SLPs. Nifurtimox Drugs and Crops: SLP phosphatases may represent future biotechnology targets SLP insensitivity to microcystin and okadaic acid combined with their complete exclusion from metazoans, but presence in select bacteria, fungi, and protozoa, renders these protein phosphatases potential therapeutic drug targets for human disease caused by SLP phosphatase containing organisms.6,7,17,20 Furthermore, the complete conservation and lack of genetic redundancy of SLP phosphatases in plants may also.