View source for Mutations in Brca1 BRCT Domains

<StructureSection load='1T15_w_HybridPeptide.pdb' size='350' side='right' caption='Human BRCA1 (blue) complex with phosphoserine-containing BRCA1 interacting protein C-terminal helicase 1 (olive) (PDB code [[1t15]])' scene='75/752201/Cv/5' pspeed='8'>
Germline mutations in the '''BRCA1 tumor suppressor''' gene often result in a significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. We report the X-ray crystal structure at a resolution of 1.85 A of the BRCA1 tandem BRCT domains in complex with a phosphorylated peptide representing the minimal interacting region of the DEAH-box helicase BACH1. The structure reveals the determinants of this novel class of BRCA1 binding events. We show that a subset of disease-linked mutations act through specific disruption of phospho-dependent BRCA1 interactions rather than through gross structural perturbation of the tandem BRCT domains.<ref>PMID: 15133502</ref>

<scene name='75/752201/Cv/4'>Brca1 BRCT domains in complex with the phosphorylated interacting region from Bach1 Helicase</scene>.

<scene name='75/752201/Cv/6'>Pathogenic and benign mutations in BRCT domain</scene>. <font color='magenta'><b>Pathogenic mutations are shown in magenta</b></font>, <font color='lime'><b>benign mutations are shown in green</b></font>, <font color='plum'><b>residues with both pathogenic and benign mutations are shown in plum</b></font>. 

==Pathogenic mutations==

*<scene name='75/752201/T1685a/4'>Mutation T1685A:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [THR]1685;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ALA]1685;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ALA]1685;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ALA]1685;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes hydrogen bonds lost.
*<scene name='75/752201/T1685i/5'>Mutation T1685I:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [THR]1685;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ILE]1685;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ILE]1685;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ILE]1685;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes hydrogen bonds lost.

*<scene name='75/752201/G1706e/4'>Mutation G1706E:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [GLY]1706;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [GLU]1706;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [GLU]1706;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [GLU]1706;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes overpacking, and forms new hydrogen bonds.
 
*<scene name='75/752201/S1715r/4'>Mutation S1715R:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [SER]1715;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ARG]1715;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ARG]1715;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ARG]1715;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes hydrogen bonds lost, overpacking.
*<scene name='75/752201/G1738r/4'>Mutation G1738R:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [GLY]1738;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ARG]1738;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ARG]1738;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ARG]1738;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes overpacking.
*<scene name='75/752201/L1764p/5'>Mutation L1764P:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [LEU]1764;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [PRO]1764;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [PRO]1764;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [PRO]1764;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes overpacking.
*<scene name='75/752201/I1766s/2'>Mutation I1766S:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [ILE]1766;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [SER]1766;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [SER]1766;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [SER]1766;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation probably decreased hydrophobic interaction. 

*<scene name='75/752201/C1787s/2'>Mutation C1787S:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [CYS]1787;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [SER]1787;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [SER]1787;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [SER]1787;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states.
*<scene name='75/752201/G1788v/4'>Mutation G1788V:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [GLY]1788;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [VAL]1788;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [VAL]1788;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [VAL]1788;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes overpacking.
*<scene name='75/752201/V1838e/1'>Mutation V1838E:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [VAL]1838;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [GLU]1838;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [GLU]1838;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [GLU]1838;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes overpacking.

=== Very severe pathogenic mutations ===
*<scene name='75/752201/R1899w/4'>Mutation R1699W:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [ARG]1699;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [TRP]1699;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [TRP]1699;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [TRP]1699;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes saltbridges lost, hydrogen bonds lost, overpacking, clashes; '''interaction lost with BRCA1 interacting protein C-terminal helicase 1'''.
*<scene name='75/752201/A1708e/4'>Mutation A1708E:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [ALA]1708;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [GLU]1708;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [GLU]1708;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [GLU]1708;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes overpacking, and forms new hydrogen bond.
*<scene name='75/752201/M1775r/10'>Mutation M1775R:</scene> 
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [MET]1775;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type</text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ARG]1775;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ARG]1775;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ARG]1775;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes interference with phosphorylated interacting region from Bach1 Helicase.
*<scene name='75/752201/M1775k/5'>Mutation M1775K:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [MET]1775;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [LYS]1775;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [LYS]1775;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [LYS]1775;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes interference with phosphorylated interacting region from Bach1 Helicase.

==Benign mutations==
*<scene name='75/752201/M1652t/1'>Mutation M1652T:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [MET]1652;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [THR]1652;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [THR]1652;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [THR]1652;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation forms the new hydrogen bond. 
*<scene name='75/752201/M1652i/1'>Mutation M1652I:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [MET]1652;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ILE]1652;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ILE]1652;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ILE]1652;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states.
*<scene name='75/752201/F1662/1'>Mutation F1662S:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [PHE]1662;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [SER]1662;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [SER]1662;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [SER]1662;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation decreased hydrophobic interaction and forms new hydrogen bonds.
*<scene name='75/752201/L1664p/1'>Mutation L1664P:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [LEU]1664;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [PRO]1664;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [PRO]1664;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [PRO]1664;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes overpacking.
*<scene name='75/752201/E1682k/1'>Mutation E1682K:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [GLU]1682;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [LYS]1682;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [LYS]1682;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [LYS]1682;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation is very interesting. There is rare interaction between 2 GLU resudues in Wild type, it is exchanged by saltbridge in the mutant.
*<scene name='75/752201/G1706a/1'>Mutation G1706A:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [GLY]1706;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ALA]1706;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ALA]1706;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ALA]1706;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. In contrast to the pathogenic mutation G1706E, this mutation causes only slight overpacking.
*<scene name='75/752201/T1720a/1'>Mutation T1720A:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [THR]1720;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ALA]1720;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ALA]1720;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ALA]1720;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes hydrogen bond lost.
*<scene name='75/752201/R1751q/1'>Mutation R1751Q:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [ARG]1751;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [GLN]1751;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [GLN]1751;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [GLN]1751;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation causes hydrogen bond lost.
*<scene name='75/752201/V1804d/1'>Mutation V1804D:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [VAL]1804;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ASP]1804;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ASP]1804;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ASP]1804;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states. This mutation forms new hydrogen bonds.
*<scene name='75/752201/I1858l/1'>Mutation I1858L:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [ILE]1858;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [LEU]1858;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [LEU]1858;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [LEU]1858;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states.
*<scene name='75/752201/P1859r/1'>Mutation P1859R:</scene>
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 1 1 play; animation off; frame 1; select [PRO]1859;color selectionHalos green;selectionHalos on;
  </script>
 <text>Wild type </text>  
 </jmolLink>
</jmol>
conformation and
<jmol>
 <jmolLink>
  <script>
    animation on; animation mode loop; frame 2 2 play; animation off; frame 2; select [ARG]1859;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutation.
  </text>
 </jmolLink>
</jmol>
Click here to see the 
<jmol>
 <jmolLink>
  <script>
    animation off; frame all; select [ARG]1859;color selectionHalos red;selectionHalos on;
  </script>
  <text>mutated and wild type
  </text>
 </jmolLink>
</jmol> residues together, and an 
<jmol>
 <jmolLink>
  <script>
   animation on; animation mode loop; frame play; select [ARG]1859;color selectionHalos red;selectionHalos on;
  </script>
  <text>animation
  </text>
 </jmolLink>
</jmol> between the two states.
</StructureSection>
== References ==
<references/>
[[Category: Disease Molecular Analysis on Proteins]]
[[Category: Molecular Pathology]]
[[Category: Protein Pathology]]
[[Category: Impact of Mutations]]
[[Category: Effect of Mutations]]