No evidence for association with APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations:

Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken a candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT

Aminoacylation at the atomic level in class IIa aminoacyl-tRNA synthetases

The crystal structures of histidyl- (HisRS) and threonyl-tRNA synthetase (ThrRS) from E. coli and glycyl-tRNA synthetase (GlyRS) from T. thermophilus, all homodimeric class IIa enzymes, were determined in enzyme-substrate and enzyme-product states corresponding to the two steps of aminoacylation. HisRS was complexed with the histidine analog histidinol plus ATP and with histidyl-adenylate, while GlyRS was complexed with ATP and with glycyl-adenylate; these complexes represent the enzyme-substrate and enzyme-product states of the first step of aminoacylation, i.e. the amino acid activation. In both enzymes the ligands occupy the substrate-binding pocket of the N-terminal active site domain, which contains the classical class II aminoacyl-tRNA synthetase fold. HisRS interacts in the same fashion with the histidine, adenosine and α-phosphate moieties of the substrates and intermediate, and GlyRS interacts in the same way with the adenosine and α-phosphate moieties in both states. In addition to the amino acid recognition, there is one key mechanistic difference between the two enzymes: HisRS uses an arginine whereas GlyRS employs a magnesium ion to catalyze the activation of the amino acid. ThrRS was complexed with its cognate tRNA and ATP, which represents the enzyme-substrate state of the second step of aminoacylation, i.e. the transfer of the amino acid to the 3′-terminal ribose of the tRNA. All three enzymes utilize class II conserved residues to interact with the adenosine-phosphate. ThrRS binds tRNA^Thr so that the acceptor stem enters the active site pocket above the adenylate, with the 3′-terminal OH positioned to pick up the amino acid, and the anticodon loop interacts with the C-terminal domain whose fold is shared by all three enzymes. We can thus extend the principles of tRNA binding to the other two enzymes