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'''Acid Base Catalysis by RNase A''' | '''Acid Base Catalysis by RNase A''' | ||
[[Image:mech.png|400px|left|thumb|Figure I: RNase A Catalysis]] | |||
In the acid base catalysis of RNA in mammalians, RNase A catalyzes the cleavage of the P-O 5’ bond, and is comprised of two separate processes, the formation of … and subsequent… An important part of the reaction is Histidine’s ability to both accept and donate electrons. This acts as a proton source, allowing Histidine to be utilized as a base or acid, making the reaction pH dependent.The catalysis of RNase A begins when His-12 undergoes basic catalysis. H-12 will act as a base and abstract a proton from the RNA’s 2’ OH group; thus, assisting the attack on the phosphorus atom. Both reactions occur via transition states having a pentavalent phosphorous atom. These transition states are both stabilized by the side chain of Lys41 and the main chain of Phe120. This leads to the formation a stabilized 2’3’-cyclic intermediate. His-119 will support this reaction by protonating the leaving group, the 6’ OH on the ribose of the 3’ RNA, thus acting as a general acid. These products are then released into the surrounding solvent. Next, the 2’,3’- cyclic nucleotide is hydrolyzed in a separate process. His-12 will donate a proton to the leaving group, the 3’ oxygen of the cyclic intermediate. Simultaneously, His-119 draws the hydrogen off of a water molecule. His 119 is thus reprotonated during this process, making water a better nucleophile. The water molecule attacks the phosphate causing the cleavage of the 2-3’ cyclic intermediate. The truncated nucleotide is then released with a 3’ phosphate group. | In the acid base catalysis of RNA in mammalians, RNase A catalyzes the cleavage of the P-O 5’ bond, and is comprised of two separate processes, the formation of … and subsequent… An important part of the reaction is Histidine’s ability to both accept and donate electrons. This acts as a proton source, allowing Histidine to be utilized as a base or acid, making the reaction pH dependent.The catalysis of RNase A begins when His-12 undergoes basic catalysis. H-12 will act as a base and abstract a proton from the RNA’s 2’ OH group; thus, assisting the attack on the phosphorus atom. Both reactions occur via transition states having a pentavalent phosphorous atom. These transition states are both stabilized by the side chain of Lys41 and the main chain of Phe120. This leads to the formation a stabilized 2’3’-cyclic intermediate. His-119 will support this reaction by protonating the leaving group, the 6’ OH on the ribose of the 3’ RNA, thus acting as a general acid. These products are then released into the surrounding solvent. Next, the 2’,3’- cyclic nucleotide is hydrolyzed in a separate process. His-12 will donate a proton to the leaving group, the 3’ oxygen of the cyclic intermediate. Simultaneously, His-119 draws the hydrogen off of a water molecule. His 119 is thus reprotonated during this process, making water a better nucleophile. The water molecule attacks the phosphate causing the cleavage of the 2-3’ cyclic intermediate. The truncated nucleotide is then released with a 3’ phosphate group. | ||