Sandbox 666: Difference between revisions

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{{STRUCTURE_1eri| PDB=1eri | SCENE= | size='500'}}     
{{STRUCTURE_1eri| PDB=1eri | SCENE= | size='500'}}     
''Eco''RI is composed of two homodimers, so it has two identical subunits (Representation of one <scene name='Sandbox_666/Monomer_structure/4'>subunit</scene>) of 31 kDa, but it is possible to have homotetramers at high concentrations. The constitutive monomers are 276 amino acids long. ''Eco''RI and all the other restriction enzymes show a common structural core, which is a α/β domain. The constitutive subunits of ''Eco''RI are organized into a single α/β domain (five strands <scene name='Sandbox_666/B_sheet/1'>β</scene> sheet, which is surrounded  by <scene name='Sandbox_666/Helix/1'>two α helices</scene> ). Four of these five β strands are parallel whereas the fourth (β4) is in an anti-parallel orientation to the others.<ref name="B">Refinement of Eco RI endonuclease crystal structure: a revised protein chain tracing.
''Eco''RI is composed of two homodimers, so it has two identical subunits (Representation of one <scene name='Sandbox_666/Monomer_structure/4'>subunit</scene>) of 31 kDa, but it is possible to have homotetramers at high concentrations. The constitutive monomers are 276 amino acids long. ''Eco''RI and all the other restriction enzymes show a common structural core, which is a α/β domain. There are several non-contiguous structural elements, whose are involved in DNA recognition<ref name="A">. The constitutive subunits of ''Eco''RI are organized into a single α/β domain (five strands <scene name='Sandbox_666/B_sheet/1'>β</scene> sheet, which is surrounded  by <scene name='Sandbox_666/Helix/1'>two α helices</scene> ). Four of these five β strands are parallel whereas the fourth (β4) is in an anti-parallel orientation to the others<ref name="B">Refinement of Eco RI endonuclease crystal structure: a revised protein chain tracing.


Kim, Y.C.,  Grable, J.C.,  Love, R.,  Greene, P.J.,  Rosenberg, J.M.,   
Kim, Y.C.,  Grable, J.C.,  Love, R.,  Greene, P.J.,  Rosenberg, J.M.,   


Journal: (1990) Science 249: 1307-1309 </ref>
Journal: (1990) Science 249: 1307-1309 </ref>. Four helices (two of each subunit) recognize the major groove and bring residues, whose interact with DNA bases and backbones.
    
    


In the old model the N-terminal section of each subunit forms the inner arm which wraps around the DNA molecule (The arm brings the DNA molecule to the catalytic cleft.).The new chain tracing, based on new elements of electron density and a new interpretation that alters the assignment of specific amino acid residues to some of the original features<ref name="B" />. In the recent model,the inner arm is the extended chain motif ('''Met<sup>137</sup>to Ala<sup>142</sup>''') is a segment of extended polypeptide chain that runs through the major groove of the DNA, roughly parallel to the DNA backbone<ref name="B" />. The outer arm is composed of two minor β strands linked together by a loop (the outer arm is 14 amino acids long, four of these amino acids belong to the loop).
In the old model, the N-terminal section of each subunit forms the inner arm, which wraps around the DNA molecule (the arm brings the DNA molecule to the catalytic cleft). In the recent model, the extended chain motif ('''Met<sup>137</sup> to Ala<sup>142</sup>''') is a segment of the extended polypeptide chain, which runs through the major groove of the DNA, roughly parallel to the DNA backbone<ref name="B" /> and forms the specific contacts of the enzymes to the DNA. The outer arm is composed of two minor β strands linked together by a loop (the outer arm is 14 amino acids long, four of these amino acids belong to the loop).
    
    
   
   
The specific recognition of ''Eco''RI of the GAATTC sequence is mediated by twelve hydrogen bonds (six bonds per subunit) originating from α helical recognition modules. Three amino acids are responsible for the recognition:'''Arg<sup>200</sup>, Glu<sup>144</sup> and Arg<sup>145</sup>'''. These aminoacids are shown in red <scene name='Sandbox_666/Grey_protein/3'>here</scene> .Each residue form two hydrogen bonds with Guanine and the adjacent Adenosine residues respectively.  
The specific recognition of ''Eco''RI of the GAATTC sequence is mediated by twelve hydrogen bonds (six bonds per subunit) originating from α helical recognition modules. Three amino acids are responsible for the recognition:'''Arg<sup>200</sup>, Glu<sup>144</sup> and Arg<sup>145</sup>'''. These amino acids are shown in red <scene name='Sandbox_666/Grey_protein/3'>here</scene>. Each residue form two hydrogen bonds with Guanine and the adjacent Adenosine residues respectively. There are also two arms, which establish contacts with DNA backbones outside the recognition sequences.
    
    
   
   
The reaction is due to a catalytic sequence motif which is found in most type II restriction endonucleases: the '''PD…(D/E)XK motif'''. For ''Eco''RI,<scene name='Sandbox_666/Catalytic_core/3'>this catalytic sequence</scene> is '''PD<sup>91</sup> …E<sup>111</sup>AK''' and the lysine residue is essential to the catalysis, but the proline residue is not important. This motif is also responsible for Mg2+ binding(Asp90 and Glu111).<ref>Structure and function of type II restriction endonucleases
There is one ß-strand parallel to the DNA backbone, which contains amino acid residues essential for catalysis (e.g.: residues engaged in phosphate contacts<ref name="A" />). The reaction is due to a catalytic sequence motif, which is found in most type II restriction endonucleases: the '''PD…(D/E)XK motif'''. For ''Eco''RI,<scene name='Sandbox_666/Catalytic_core/3'>this catalytic sequence</scene> is '''PD<sup>91</sup> …E<sup>111</sup>AK''' and the lysine residue is essential to the catalysis, but the proline residue is not important. This motif is also responsible for Mg<sup>2+</sup> binding (Asp90 and Glu111)<ref>Structure and function of type II restriction endonucleases
Alfred Pingoud, Albert Jeltsch
Alfred Pingoud, Albert Jeltsch
Nucleic Acids Res. 2001 September 15; 29(18): 3705–3727.
Nucleic Acids Res. 2001 September 15; 29(18): 3705–3727.
PMCID: PMC55916</ref>
PMCID: PMC55916</ref>.


There are several non-contiguous structural elements, which are involved in DNA recognition<ref name="A" />:
* Four helix (two of each subunit) recognize the major groove and bring residues, whose interact with DNA bases and backbones
* An extended peptide chain running through the major groove forms the specific contacts of the enzymes to the DNA.
* One ß-strand parallel to the DNA backbone, which contains amino acid residues essential for catalysis (e.g.: residues engaged in phosphate contacts)
* Two arms, which establish contacts with DNA backbones outside the recognition sequences.


This binding by the major groove is due to the position of scissile phosphodiester bonds.<ref name="A">Recognition and cleavage of DNA by type-II restriction endonucleases, Pingoud A. & Jeltsch A. Eur.J.Biochem. 246,1-22 (1997)</ref>
This binding by the major groove is due to the position of scissile phosphodiester bonds.<ref name="A">Recognition and cleavage of DNA by type-II restriction endonucleases, Pingoud A. & Jeltsch A. Eur.J.Biochem. 246,1-22 (1997)</ref>