RNase A: Difference between revisions
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==='''Active Site Structure'''=== | ==='''Active Site Structure'''=== | ||
[[Image:MechIII.png| | [[Image:MechIII.png|400px|left|thumb|Figure II: RNase A Catalysis. (A) Initial attack of 2'hydroxyl stabilized by His12. (B) Pentavalent phosphorous intermediate. (C) 2'3' cyclic intermediate degradation. (D) Finished products: Two distinctive nucleotide sequences. Figure generated via ''Chemdraw'']] | ||
RNase A uses acid/base catlysis to speed up RNA hydrolysis. This occurs in the <scene name='Sandbox_Reserved_193/Active_site_a/1'>active site</scene> which is found in the cleft of RNase A and is the location of the chemical change in bound substrates. Subsites lining the active site cleft are important to the binding of single stranded RNA. Large quantities of positively charged residues, such as <scene name='Sandbox_Reserved_193/Lys7_arg10_arg39_lys41_lys66/1'>Lys7, Arg10, Arg39, and Lys41, and Lys66</scene>, recognize the negative charge on the phosphate back bone of the <scene name='Sandbox_Reserved_194/Positive_amino_acids_substrate/1'>RNA strand</scene> <ref name="Wlodrawer" />. | |||
The active site for RNase A, although fairly nonspecific, has some specificity for sites RNA hydrolysis. <scene name='Sandbox_Reserved_193/Thr45_a/1'>Threonine 45</scene>, located next to the active site, will hydrogen bond to pyrimidine bases, but sterically hinder the binding of a purine on the 5' strand of OH. Thr45 significantly decreases the rate of hydrolysis of polymeric purine strands, such as poly A, by a thousand fold, as compared to polymeric pyrimidine strands.<ref name = 'Wlodrawer'>PMID:3401445</ref> | The active site for RNase A, although fairly nonspecific, has some specificity for sites RNA hydrolysis. <scene name='Sandbox_Reserved_193/Thr45_a/1'>Threonine 45</scene>, located next to the active site, will hydrogen bond to pyrimidine bases, but sterically hinder the binding of a purine on the 5' strand of OH. Thr45 significantly decreases the rate of hydrolysis of polymeric purine strands, such as poly A, by a thousand fold, as compared to polymeric pyrimidine strands.<ref name = 'Wlodrawer'>PMID:3401445</ref> | ||
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From the studies on RNase A complexes with deoxy nucleic acid tetramers, it has been established that this enzyme recognizes the substrate on both its phosphate backbone and on individual nucleobases. RNase A has a nonspecific B0 site, a B1 site specific to pyrimidines and a B3 and B4 site with a preference for adenosine bases. Similar to other enzymes, RNase A uses the hydrogen bonding distance between amino acids and the substrate to bind specifically to certain nucleobases. Studying the substrate recognition and specificity of enzymes such as RNase A is an important step in understanding the regulation of RNA within biological systems. | From the studies on RNase A complexes with deoxy nucleic acid tetramers, it has been established that this enzyme recognizes the substrate on both its phosphate backbone and on individual nucleobases. RNase A has a nonspecific B0 site, a B1 site specific to pyrimidines and a B3 and B4 site with a preference for adenosine bases. Similar to other enzymes, RNase A uses the hydrogen bonding distance between amino acids and the substrate to bind specifically to certain nucleobases. Studying the substrate recognition and specificity of enzymes such as RNase A is an important step in understanding the regulation of RNA within biological systems. | ||
=='''Inhibitors'''== | =='''Inhibitors'''== | ||
<scene name='User:R._Jeremy_Johnson/RNaseA/Ri_rnasea_simple/1'>inhibitor (RI) (tan) bound to RNase A (red)</scene> ([[1dfj]]). | <scene name='User:R._Jeremy_Johnson/RNaseA/Ri_rnasea_simple/1'>inhibitor (RI) (tan) bound to RNase A (red)</scene> ([[1dfj]]). | ||
