The kinomes of apicomplexan parasites

Abstract

Protein phosphorylation plays a fundamental role in the biology and invasion strategies of apicomplexan parasites. Many apicomplexan protein kinases are substantially different from their mammalian orthologues, and thus constitute a landscape of potential drug targets. Here, we integrate genomic, biochemical, genetic and evolutionary information to provide an integrated and up-to-date analysis of twelve apicomplexan kinomes. All kinome sequences are available through the Kinomer database.2

<em>Sarcocystis neurona</em> Protein Kinases: Computational Identification, Evolutionary Analysis and Putative Inhibitor Docking

“…The CMGC is the largest PK group in apicomplexans; CMGC numbers range from 15 in B. bovis to 23 in P. vivax [15], which is within the range we identified in the S. neurona kinome in our study (i.e. 19 CMGCs; See Table 1).…”

“…Available data show that CDKs are essential in P. falciparum [35]. We also identified two putative MAPK homologs (SRCN_4209 and SRCN_5365), and ERK7 (SRCN_6472) (see Table 1), a result which is comparable to the two MAPKs in the kinome of P. falciparum [15].…”

“…The numbers of apicomplexan AGCs range from four (in B. bovis) to 15 (in T. gondii) [15]. Based on our Blast2GO annotations and BLASTp homology searches against the kinome database, five out of the nine S. neurona AGCs (SRCN_3339, SRCN_3990, SRCN_5165, SRCN_5610 and SRCN_1312) were homologs to the universally conserved PKAs that are found in N. caninum and T. gondii (see Table 1).…”

“…Apicomplexan kinomes constitute varying numbers of CAMKs, which range from seven (in B. bovis) to 29 (in T. gondii) [15]. The most important CAMK family is the CDPK, which appeared to constitute almost 50% of S. neurona putative CAMKs (See Table 1).…”

“…Apart from T. gondii and some alveolates (e.g. Cryptosporidium hominis and C. parvum, important causative agents of diarrhea in children), which have three and two CK1 enzymes, respectively, most apicomplexans possess a single CK1 enzyme [15]. Two of the three S. neurona putative CK1 (SRCN_3445 and SRCN_4645) showed high sequence similarity (>90%) to the T. gondii TME49_040640 (TgCK1-α) and TGME49_089320 (TgCK1-β), respectively ( Table 1).…”