Attenuating the function of protein arginine methyltransferases (PRMTs) is an objective for the investigation and treatment of several diseases including cardiovascular disease and cancer. Bisubstrate inhibitors that simultaneously target binding sites for arginine substrate and the cofactor (S-adenosylmethionine (SAM)) have potential utility, but structural information on their binding is required for their development. Evaluation of bisubstrate inhibitors featuring an isosteric guanidine replacement with two prominent enzymes PRMT1 and CARM1 (PRMT4) by isothermal titration calorimetry (ITC), activity assays and crystallography are reported. Key findings are that 2-aminopyridine is a viable replacement for guanidine, providing an inhibitor that binds more strongly to CARM1 than PRMT1. Moreover, a residue around the active site that differs between CARM1 (Asn-265) and PRMT1 (Tyr-160) is identified that affects the side chain conformation of the catalytically important neighbouring glutamate in the crystal structures. Mutagenesis data supports its contribution to the difference in binding observed for this inhibitor. Structures of CARM1 in complex with a range of seven inhibitors reveal the binding modes and show that inhibitors with an amino acid terminus adopt a single conformation whereas the electron density for equivalent amine-bearing inhibitors is consistent with preferential binding in two conformations. These findings inform the molecular basis of CARM1 ligand binding and identify differences between CARM1 and PRMT1 that can inform drug discovery efforts.

Dyslipidemia is a pathological condition in which lipids profile and blood proteins are in abnormal proportions and is associated with many diseases and has major complications such as cardiovascular diseases that are linked to high HDL and risk factors increase, especially in young people, and there may be a link between chronic diseases and high fat percentage , 1482blood samples were collected for children aged between (2-17) years for both sexes and separated by centrifuge device to measure the percentage of total body fat. The measurements for the fat of Iraqi male children showed (>25%) of elevated TC, and (>27%) in female population, also over 45% of the male and 30% of female population have had an elevated TG, While all male population had a low HDL only (61%) of the female population were in the high risk category. All these percentage indicates a high lipid profile among pediatrics which in turn makes huge health problems in the general health of future young especially cardiovascular diseases. Finally a routine lipid profile work should be done since the age of 9 or less according to the individual health and nutrition and that is what the National Cholesterol Education Program has recommended.