Arginine methylations can regulate {important|essential|crucial|critical|significant|vital} biological processes and {affect|impact|have an effect on|influence} {many|numerous|several|a lot of|quite a few|lots of} cellular activities, {and the|and also the|as well as the|along with the|plus the} enzymes that catalyze the methylations are protein arginine methyltransferases (PRMTs). The biological consequences of arginine methylations {depend on|rely on} the methylation states of arginine {that are|which are|which can be|which might be|that happen to be} determined by the PRMT’s {product|item|solution} specificity. {Although|Even though|Though|Despite the fact that|While} the {product|item|solution} specificity {is a|is really a|is actually a|can be a|is often a|is usually a} {very important|essential|crucial} {property|home|house}, {it is|it’s|it really is|it truly is|it can be|it is actually} {still|nonetheless|nevertheless} unknown {concerning|regarding} why {different|various|distinct|diverse|unique|distinctive} PRMTs {may|might|could|may possibly|may well|may perhaps} {generate|produce|create} {different|various|distinct|diverse|unique|distinctive} methylation states for the target arginine residues on protein substrates. PRMT7 {is the|will be the|may be the|would be the|could be the|is definitely the} only {known|recognized|identified} member of {Type|Kind|Sort|Variety|Form} III PRMT that produces mono-methylarginine (MMA) {product|item|solution}. Interestingly, its E181D and E181D/Q329A mutants can catalyze, respectively, the formation of asymmetrically di-methylated arginine (ω-NG, NG-dimethylarginine or ADMA) and symmetrically di-methylated arginine (ω-NG, N’G-dimethylarginine or SDMA). The {exact|precise} {reasons|factors|causes|motives} for such {product|item|solution} specificity modification {as a result|consequently|because of this} {of the|from the|in the|on the|with the|of your} mutations {have been|happen to be|have already been} unclear. {Here|Right here} QM/MM molecular dynamics (MD) and {potential|possible|prospective} of {mean|imply} force (PMF) free-energy simulations are performed for the E181D and E181D/Q329A mutants {to understand|to know} the catalytic mechanism {and the|and also the|as well as the|along with the|plus the} origin of their {different|various|distinct|diverse|unique|distinctive} {product|item|solution} specificities from that {of the|from the|in the|on the|with the|of your} wild-type PRMT7 {as well|also|too|at the same time} as {between|in between|among|amongst|involving} E181D and E181D/Q329A. The simulations show that {while|whilst|although|even though|when|though} the {free|totally free|free of charge|cost-free|absolutely free|no cost} {energy|power} barriers of E181D and E181D/Q329A for {the first|the very first|the initial} methylation are {higher|greater|larger} than that {of the|from the|in the|on the|with the|of your} wild {type|kind|sort|variety|form}, E181D and E181D/Q329A {have the|possess the} {ability to|capability to} add the second methyl group {to the|towards the|for the} target mono-methyl arginine and {generate|produce|create} ADMA and SDMA, respectively. The {free|totally free|free of charge|cost-free|absolutely free|no cost} {energy|power} barriers for E181D and E181D/Q329A to {produce|create|generate|make} ADMA and SDMA, respectively, are {considerably|significantly} {lower|reduce|reduced|decrease} than the corresponding barriers involving the wild-type enzyme. {Moreover|Furthermore|In addition|Additionally}, the computational study identifies some {important|essential|crucial|critical|significant|vital} structural, electronic and dynamic {features|attributes|functions|characteristics|capabilities|options} that {lead to|result in|bring about|cause} the {different|various|distinct|diverse|unique|distinctive} {product|item|solution} specificities and activities {of the|from the|in the|on the|with the|of your} wild-type PRMT7, E181D and E181D/Q329A. These {factors|elements|aspects|variables|components|things} {may|might|could|may possibly|may well|may perhaps} play {important|essential|crucial|critical|significant|vital} roles in controlling the activity and {product|item|solution} specificity of other PRMTs {as well|also|too|at the same time}. 945459-80-3 Chemscene XPhos Pd G2 Chemical name PMID:34235739
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