79 nmol/min) it is more than twice that showed by the isoforms Lm

79 nmol/min) it is more than twice that showed by the isoforms LmTX-I and LmTX-II (6.1 nmol/min and 5.7 nmol/min, respectively). Both data clearly

indicate that exits some degree of structural differences between these proteins. Along with the biochemical Palbociclib supplier data, the molecular mass of LmrTX (14,277.50 Da) is different from LmTX-I and LmTX-II (14,245.4 and 14,186.2, respectively). The molecular mass difference found is in accordance with the aminoacid composition, which shown variation in the number of Pro, Thr and Ala residues. Despite the biochemical and structural differences between LmrTX and the isoforms LmTX-I and LmTX-II, the high degree of identity suggest that this toxin

could exert similar pharmacologic activities, i.e neurotoxic activity ex vivo. Phospholipase enzymes can exert their anticoagulant effects by the hydrolysis and physical destruction of the membrane surface required Ruxolitinib for the formation of coagulation complexes or by their interaction with blood coagulation proteins and not phospholipid hydrolysis (Kini, 2005). APTT is used to measure the integrity of components of the intrinsic pathaway and PT measures the integrity of the extrinsic pathaway. LmrTx interfered only with APTT, prolonging this time. The protein could be acting in the enzymatic cleavage of the available phospholipids required to intrinsic pathaway, since it was seen that chemical modification of histidine residues neutralized its anticoagulant activity. Based on the comparison of the three dimensional structure of class II PLA2 enzymes, three independent groups supported the predicted anticoagulant site (Carredano et al., 1998; Zhao et al., 2000; Singh et al., 2001). This region shows conformational

similarity and the presence of positively charged residue free for intermolecular interactions at the corner of molecule corresponding to the stretch of residues 55–67 seems to be a common feature of most of the anticoagulant PLA2 enzymes (Carredano et al., 1998; Zhao et al., 2000; Singh et al., 2001). For the RVV-VD, a PLA2 from the venom of Russell’s viper (Vipera russeli russeli), a strong Montelukast Sodium anticoagulant PLA2 of this class, this region has several lysine residues ( Carredano et al., 1998). In LmrTx this region has not been fully determined, only two residues positively charged in this segment was showed, which are favorably oriented to induce the anticoagulant effect. When performing chemical modification of histidine residues (alkylation with p-bromophenacyl bromide), LmrTX showed a reduction in its catalytic activity in 89% and there was an inactivation of the anticoagulant activity. The present study supports that anticoagulant activity in vitro of LmrTX is dependent on its catalytic activity.

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