User:R. Jeremy Johnson/RNaseA: Difference between revisions

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='''Structure'''=

='''Structure'''= {{STRUCTURE_7rsa | PDB=7RSA | SCENE= Sandbox_Reserved_193/Rnasei_a/1 }}RNase A is made up of a single polypeptide chain of 124 residues. Of the 20 natural amino acids, RNase A possesses 19 of them, excluding tryptophan. This single polypeptide chain is cross-linked internally by four disulfide linkages, which contribute to the stability of RNase A. Long four-stranded anti-parallel <scene name='Sandbox_Reserved_192/Beta_sheet/4'>ß-sheets</scene> and three short <scene name='Sandbox_Reserved_192/Alpha_helices/2'>α-helices</scene> make up the <scene name='Sandbox_Reserved_192/Secondary_structure/3'>secondary structure</scene> of RNase A (Raines). The amino acid sequence was discovered to determine the three-dimensional structure of RNase A by Christian Anfinsen in the 1950s. Urea was used to denature RNase A, and mercaptoethanol was used to reduce and cleave the four disulfide bonds in RNase A to yield eight Cys residues. Catalytic activity was lost due to denaturation. When the urea and mercaptoethanol were removed, the denatured ribonuclease refolded spontaneously into its correct tertiary structure with restoration of its catalytic activity. Disulfide bonds were also reformed in the same position. The Anfinsen experiment provided evidence that the amino acid sequence contained all the information required for the protein to fold into its native three-dimensional structure. Anfinsen received the 1972 Nobel Prize in Chemistry for his work with RNase A. Nevertheless, ensuing work showed some proteins require further assistance, such as molecular chaperones, to fold into their native structure.

{{STRUCTURE_7rsa | PDB=7RSA | SCENE= Sandbox_Reserved_193/Rnasei_a/1 }}RNase A is made up of a single polypeptide chain of 124 residues. Of the 20 natural amino acids, RNase A possesses 19 of them, excluding tryptophan. This single polypeptide chain is cross-linked internally by four disulfide linkages, which contribute to the stability of RNase A. Long four-stranded anti-parallel <scene name='Sandbox_Reserved_192/Beta_sheet/4'>ß-sheets</scene> and three short <scene name='Sandbox_Reserved_192/Alpha_helices/2'>α-helices</scene> make up the <scene name='Sandbox_Reserved_192/Secondary_structure/3'>secondary structure</scene> of RNase A (Raines). The amino acid sequence was discovered to determine the three-dimensional structure of RNase A by Christian Anfinsen in the 1950s. Urea was used to denature RNase A, and mercaptoethanol was used to reduce and cleave the four disulfide bonds in RNase A to yield eight Cys residues. Catalytic activity was lost due to denaturation. When the urea and mercaptoethanol were removed, the denatured ribonuclease refolded spontaneously into its correct tertiary structure with restoration of its catalytic activity. Disulfide bonds were also reformed in the same position. The Anfinsen experiment provided evidence that the amino acid sequence contained all the information required for the protein to fold into its native three-dimensional structure. Anfinsen received the 1972 Nobel Prize in Chemistry for his work with RNase A. Nevertheless, ensuing work showed some proteins require further assistance, such as molecular chaperones, to fold into their native structure.

='''Ribonuclease A Catalysis'''=

=='''Acid Base Catalysis'''==

In organic chemistry acid/base catalysis is the addition of an acid or base to accelerate a chemical reaction. Ribonuclease A, (RNase A), also uses acid/base catatalysis to chemically change its substrates. Acidic or basic residues of the enzyme transfer protons to or from the reactant in order to stabilize the developing charges in the transition state. The transfer of protons usually creates better leaving groups, making the reaction more energetically favorable. Histidine is a very common amino acid residue involved in cataylsis, as histidine has a pKa value close to neutral, (p''K''a=6); therefore, histidine can both accept and donate protons at physiological pH.

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RNase A is an endonuclease that cleaves and breaks down RNA using acid base catalysis. RNase A has been a model protein for studies on the stability, folding and chemistry of proteins. ‘<ref>PMID:11848924</ref>’ It is also essential in protein regulation within the body due to its function of RNA degradation.

~~== Substrate Binding ==~~

== Substrate Binding ==<Structure load='1RTA' size='350' frame='true' align='right' caption='Ribonuclease A complexed with thymidylic acid tetramer and ApTpApApG showing pi stacking and hydrogen bonding' scene='Sandbox_Reserved_194/1rta_structure/2'/>

[[Image:1RTAnew.png|thumb|left|280px|Thymidylic acid tetramer complexed with ribonuclease A]]

@@ Line 8: / Line 8: @@
-='''Structure'''=
+='''Structure'''= {{STRUCTURE_7rsa |  PDB=7RSA |  SCENE= Sandbox_Reserved_193/Rnasei_a/1 }}RNase A is made up of a single polypeptide chain of 124 residues. Of the 20 natural amino acids, RNase A possesses 19 of them, excluding tryptophan. This single polypeptide chain is cross-linked internally by four disulfide linkages, which contribute to the stability of RNase A. Long four-stranded anti-parallel <scene name='Sandbox_Reserved_192/Beta_sheet/4'>ß-sheets</scene> and three short <scene name='Sandbox_Reserved_192/Alpha_helices/2'>α-helices</scene> make up the <scene name='Sandbox_Reserved_192/Secondary_structure/3'>secondary structure</scene> of RNase A (Raines). The amino acid sequence was discovered to determine the three-dimensional structure of RNase A by Christian Anfinsen in the 1950s. Urea was used to denature RNase A, and mercaptoethanol was used to reduce and cleave the four disulfide bonds in RNase A to yield eight Cys residues. Catalytic activity was lost due to denaturation. When the urea and mercaptoethanol were removed, the denatured ribonuclease refolded spontaneously into its correct tertiary structure with restoration of its catalytic activity. Disulfide bonds were also reformed in the same position. The Anfinsen experiment provided evidence that the amino acid sequence contained all the information required for the protein to fold into its native three-dimensional structure. Anfinsen received the 1972 Nobel Prize in Chemistry for his work with RNase A. Nevertheless, ensuing work showed some proteins require further assistance, such as molecular chaperones, to fold into their native structure.
-{{STRUCTURE_7rsa |  PDB=7RSA |  SCENE= Sandbox_Reserved_193/Rnasei_a/1 }}RNase A is made up of a single polypeptide chain of 124 residues. Of the 20 natural amino acids, RNase A possesses 19 of them, excluding tryptophan. This single polypeptide chain is cross-linked internally by four disulfide linkages, which contribute to the stability of RNase A. Long four-stranded anti-parallel <scene name='Sandbox_Reserved_192/Beta_sheet/4'>ß-sheets</scene> and three short <scene name='Sandbox_Reserved_192/Alpha_helices/2'>α-helices</scene> make up the <scene name='Sandbox_Reserved_192/Secondary_structure/3'>secondary structure</scene> of RNase A (Raines). The amino acid sequence was discovered to determine the three-dimensional structure of RNase A by Christian Anfinsen in the 1950s. Urea was used to denature RNase A, and mercaptoethanol was used to reduce and cleave the four disulfide bonds in RNase A to yield eight Cys residues. Catalytic activity was lost due to denaturation. When the urea and mercaptoethanol were removed, the denatured ribonuclease refolded spontaneously into its correct tertiary structure with restoration of its catalytic activity. Disulfide bonds were also reformed in the same position. The Anfinsen experiment provided evidence that the amino acid sequence contained all the information required for the protein to fold into its native three-dimensional structure. Anfinsen received the 1972 Nobel Prize in Chemistry for his work with RNase A. Nevertheless, ensuing work showed some proteins require further assistance, such as molecular chaperones, to fold into their native structure.
 ='''Ribonuclease A Catalysis'''=
 =='''Acid Base Catalysis'''==
 In organic chemistry acid/base catalysis is the addition of an acid or base to accelerate a chemical reaction. Ribonuclease A, (RNase A), also uses acid/base catatalysis to chemically change its substrates. Acidic or basic residues of the enzyme transfer protons to or from the reactant in order to stabilize the developing charges in the transition state. The transfer of protons usually creates better leaving groups, making the reaction more energetically favorable. Histidine is a very common amino acid residue involved in cataylsis, as histidine has a pKa value close to neutral, (p''K''a=6); therefore, histidine can both accept and donate protons at physiological pH.
@@ Line 38: / Line 36: @@
 RNase A is an endonuclease that cleaves and breaks down RNA using acid base catalysis. RNase A has been a model protein for studies on the stability, folding and chemistry of proteins. ‘<ref>PMID:11848924</ref>’ It is also essential in protein regulation within the body due to its function of RNA degradation.
-<Structure load='1RTA' size='350' frame='true' align='right' caption='Ribonuclease A complexed with thymidylic acid tetramer and ApTpApApG showing pi stacking and hydrogen bonding' scene='Sandbox_Reserved_194/1rta_structure/2'/>
-== Substrate Binding ==
+== Substrate Binding ==<Structure load='1RTA' size='350' frame='true' align='right' caption='Ribonuclease A complexed with thymidylic acid tetramer and ApTpApApG showing pi stacking and hydrogen bonding' scene='Sandbox_Reserved_194/1rta_structure/2'/>
 [[Image:1RTAnew.png|thumb|left|280px|Thymidylic acid tetramer complexed with ribonuclease A]]