GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains unclear. Crystal structures of Plasmodium falciparum GMPS in conjunction with mutational and enzyme kinetic studies reported here provide evidence that an 85° rotation of the GATase domain is required for ammonia channelling and thus for the catalytic activity of this two-domain enzyme. We suggest that conformational changes in helix 371–375 holding catalytic residues and in loop 376–401 along the rotation trajectory trigger the different steps of catalysis, and establish the central role of Glu374 in allostery and inter-domain crosstalk. These studies reveal the mechanism of domain rotation and inter-domain communication, providing a molecular framework for the function of all single polypeptide GMPSs and form a solid basis for rational drug design targeting this therapeutically important enzyme.

Morinda citrifolia (Noni) is a medicinal plant widely distributed in the tropical regions of India, Indonesia and Malaysia and has a long history of treating a wide variety of diseases such as cancer, atherosclerosis and diabetes. The present investigation was designed to evaluate blood biochemical parameters and antioxidant effects in calves fed with M. citrifolia. A total of eight calves were divided into two groups as control (n = 4) and treatment (n = 4). The calves of treatment group were fed with fresh minced raw fruit (100 g/calf/day) and the calves in control group were fed with placebo. Blood samples were collected at weekly intervals for four weeks for estimation of biochemical parameters and to determine antioxidant activity. The crude extract of noni fruits significantly (P < .01) decreased the concentrations of serum total cholesterol, triglycerides, serum glucose and also decreased (P < .05) serum creatinine and urea. There was a reduction in lipid peroxidation (LPO) than control; however, superoxide dismutase (SOD) and catalase levels were dramatically increased (P < .01) in morinda-fed calves. The results of present preliminary study demonstrated hypolipidemic, hypoglycaemic and antioxidant effect of M. citrifolia in calves. The findings of this study could be exploited for stress amelioration and management of metabolic diseases in calves and cattle without adverse effects.

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