char = I;code = 73 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = f;code = 102 char = l;code = 108 char = e;code = 101 char = x;code = 120 char = i;code = 105 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = ;code = 32 char = 2;code = 50 char = -;code = 45 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = r;code = 114 char = o;code = 111 char = g;code = 103 char = l;code = 108 char = o;code = 111 char = b;code = 98 char = u;code = 117 char = l;code = 108 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = u;code = 117 char = p;code = 112 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = p;code = 112 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = :;code = 58 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = s;code = 115 char = s;code = 115 char = i;code = 105 char = b;code = 98 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = p;code = 112 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = a;code = 97 char = l;code = 108 char = y;code = 121 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = -;code = 45 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = m;code = 109 char = y;code = 121 char = l;code = 108 char = o;code = 111 char = i;code = 105 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = .;code = 46 result sql = Increase in the conformational flexibility of beta 2-microglobulin upon copper binding: a possible role for copper in dialysis-related amyloidosis.
Increase in the conformational flexibility of beta 2-microglobulin upon copper binding: a possible role for copper in dialysis-related amyloidosis.char = A;code = 65 char = ;code = 32 char = k;code = 107 char = e;code = 101 char = y;code = 121 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = h;code = 104 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = a;code = 97 char = l;code = 108 char = y;code = 121 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = -;code = 45 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = m;code = 109 char = y;code = 121 char = l;code = 108 char = o;code = 111 char = i;code = 105 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = i;code = 105 char = b;code = 98 char = r;code = 114 char = i;code = 105 char = l;code = 108 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = (;code = 40 char = 2;code = 50 char = );code = 41 char = -;code = 45 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = r;code = 114 char = o;code = 111 char = g;code = 103 char = l;code = 108 char = o;code = 111 char = b;code = 98 char = u;code = 117 char = l;code = 108 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = (;code = 40 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = ;code = 32 char = 2;code = 50 char = -;code = 45 char = m;code = 109 char = );code = 41 char = .;code = 46 char = ;code = 32 char = B;code = 66 char = e;code = 101 char = c;code = 99 char = a;code = 97 char = u;code = 117 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = ;code = 32 char = 2;code = 50 char = -;code = 45 char = m;code = 109 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = t;code = 116 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = ;code = 32 char = f;code = 102 char = i;code = 105 char = b;code = 98 char = r;code = 114 char = i;code = 105 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = ,;code = 44 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = c;code = 99 char = e;code = 101 char = p;code = 112 char = t;code = 116 char = ;code = 32 char = u;code = 117 char = n;code = 110 char = d;code = 100 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = i;code = 105 char = s;code = 115 char = p;code = 112 char = o;code = 111 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = o;code = 111 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = d;code = 100 char = r;code = 114 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = i;code = 105 char = b;code = 98 char = r;code = 114 char = i;code = 105 char = l;code = 108 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = p;code = 112 char = h;code = 104 char = y;code = 121 char = s;code = 115 char = i;code = 105 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = p;code = 112 char = H;code = 72 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = c;code = 99 char = u;code = 117 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = m;code = 109 char = u;code = 117 char = c;code = 99 char = h;code = 104 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = t;code = 116 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = .;code = 46 char = ;code = 32 char = O;code = 79 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = m;code = 109 char = p;code = 112 char = l;code = 108 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = C;code = 67 char = u;code = 117 char = (;code = 40 char = 2;code = 50 char = +;code = 43 char = );code = 41 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ,;code = 44 char = ;code = 32 char = w;code = 119 char = h;code = 104 char = i;code = 105 char = c;code = 99 char = h;code = 104 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = z;code = 122 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = n;code = 110 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = ;code = 32 char = 2;code = 50 char = -;code = 45 char = m;code = 109 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = u;code = 117 char = s;code = 115 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = z;code = 122 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = m;code = 109 char = y;code = 121 char = l;code = 108 char = o;code = 111 char = i;code = 105 char = d;code = 100 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = c;code = 99 char = u;code = 117 char = r;code = 114 char = s;code = 115 char = o;code = 111 char = r;code = 114 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = d;code = 100 char = d;code = 100 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = C;code = 67 char = u;code = 117 char = (;code = 40 char = 2;code = 50 char = +;code = 43 char = );code = 41 char = -;code = 45 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = z;code = 122 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = ;code = 32 char = 2;code = 50 char = -;code = 45 char = m;code = 109 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = o;code = 111 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = l;code = 108 char = ,;code = 44 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = u;code = 117 char = d;code = 100 char = i;code = 105 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = c;code = 99 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = g;code = 103 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = d;code = 100 char = y;code = 121 char = n;code = 110 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = ;code = 32 char = 2;code = 50 char = -;code = 45 char = m;code = 109 char = ;code = 32 char = u;code = 117 char = p;code = 112 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = C;code = 67 char = u;code = 117 char = (;code = 40 char = 2;code = 50 char = +;code = 43 char = );code = 41 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = ;code = 32 char = 2;code = 50 char = -;code = 45 char = m;code = 109 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = C;code = 67 char = u;code = 117 char = (;code = 40 char = 2;code = 50 char = +;code = 43 char = );code = 41 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = n;code = 110 char = i;code = 105 char = t;code = 116 char = o;code = 111 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = b;code = 98 char = y;code = 121 char = ;code = 32 char = h;code = 104 char = e;code = 101 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = u;code = 117 char = c;code = 99 char = l;code = 108 char = e;code = 101 char = a;code = 97 char = r;code = 114 char = ;code = 32 char = N;code = 78 char = M;code = 77 char = R;code = 82 char = ;code = 32 char = s;code = 115 char = h;code = 104 char = o;code = 111 char = w;code = 119 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = r;code = 114 char = e;code = 101 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = u;code = 117 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = u;code = 117 char = r;code = 114 char = ;code = 32 char = h;code = 104 char = i;code = 105 char = s;code = 115 char = t;code = 116 char = i;code = 105 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = (;code = 40 char = H;code = 72 char = i;code = 105 char = s;code = 115 char = 1;code = 49 char = 3;code = 51 char = ,;code = 44 char = ;code = 32 char = H;code = 72 char = i;code = 105 char = s;code = 115 char = 3;code = 51 char = 1;code = 49 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = H;code = 72 char = i;code = 105 char = s;code = 115 char = 5;code = 53 char = 1;code = 49 char = );code = 41 char = ;code = 32 char = a;code = 97 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = v;code = 118 char = o;code = 111 char = l;code = 108 char = v;code = 118 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = p;code = 112 char = H;code = 72 char = ;code = 32 char = 7;code = 55 char = .;code = 46 char = 0;code = 48 char = .;code = 46 char = ;code = 32 char = (;code = 40 char = 1;code = 49 char = );code = 41 char = H;code = 72 char = -;code = 45 char = (;code = 40 char = 1;code = 49 char = 5;code = 53 char = );code = 41 char = N;code = 78 char = ;code = 32 char = h;code = 104 char = e;code = 101 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = u;code = 117 char = c;code = 99 char = l;code = 108 char = e;code = 101 char = a;code = 97 char = r;code = 114 char = ;code = 32 char = N;code = 78 char = O;code = 79 char = E;code = 69 char = ;code = 32 char = s;code = 115 char = u;code = 117 char = g;code = 103 char = g;code = 103 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = b;code = 98 char = a;code = 97 char = c;code = 99 char = k;code = 107 char = b;code = 98 char = o;code = 111 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = d;code = 100 char = y;code = 121 char = n;code = 110 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = s;code = 115 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = d;code = 100 char = u;code = 117 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = V;code = 86 char = a;code = 97 char = l;code = 108 char = 4;code = 52 char = 9;code = 57 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = S;code = 83 char = e;code = 101 char = r;code = 114 char = 5;code = 53 char = 5;code = 53 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = m;code = 109 char = p;code = 112 char = l;code = 108 char = y;code = 121 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = C;code = 67 char = u;code = 117 char = (;code = 40 char = 2;code = 50 char = +;code = 43 char = );code = 41 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = H;code = 72 char = i;code = 105 char = s;code = 115 char = 5;code = 53 char = 1;code = 49 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = o;code = 111 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = d;code = 100 char = y;code = 121 char = n;code = 110 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = c;code = 99 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = -;code = 45 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = D;code = 68 char = .;code = 46 char = ;code = 32 char = H;code = 72 char = y;code = 121 char = d;code = 100 char = r;code = 114 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = /;code = 47 char = d;code = 100 char = e;code = 101 char = u;code = 117 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = u;code = 117 char = m;code = 109 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = c;code = 99 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = g;code = 103 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = d;code = 100 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = t;code = 116 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = ;code = 32 char = s;code = 115 char = h;code = 104 char = o;code = 111 char = w;code = 119 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = l;code = 108 char = e;code = 101 char = x;code = 120 char = i;code = 105 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = d;code = 100 char = u;code = 117 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = u;code = 117 char = p;code = 112 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = C;code = 67 char = u;code = 117 char = (;code = 40 char = 2;code = 50 char = +;code = 43 char = );code = 41 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = a;code = 97 char = k;code = 107 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = r;code = 114 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = l;code = 108 char = i;code = 105 char = k;code = 107 char = e;code = 101 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = C;code = 67 char = u;code = 117 char = (;code = 40 char = 2;code = 50 char = +;code = 43 char = );code = 41 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = i;code = 105 char = c;code = 99 char = o;code = 111 char = -;code = 45 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = n;code = 110 char = a;code = 97 char = n;code = 110 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = l;code = 108 char = u;code = 117 char = c;code = 99 char = t;code = 116 char = u;code = 117 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = -;code = 45 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = D;code = 68 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = w;code = 119 char = h;code = 104 char = i;code = 105 char = c;code = 99 char = h;code = 104 char = ;code = 32 char = H;code = 72 char = i;code = 105 char = s;code = 115 char = 5;code = 53 char = 1;code = 49 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = i;code = 105 char = s;code = 115 char = t;code = 116 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = w;code = 119 char = h;code = 104 char = i;code = 105 char = c;code = 99 char = h;code = 104 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = p;code = 112 char = a;code = 97 char = g;code = 103 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = c;code = 99 char = u;code = 117 char = l;code = 108 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = u;code = 117 char = s;code = 115 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = m;code = 109 char = o;code = 111 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = g;code = 103 char = l;code = 108 char = o;code = 111 char = b;code = 98 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = s;code = 115 char = l;code = 108 char = o;code = 111 char = w;code = 119 char = ;code = 32 char = f;code = 102 char = l;code = 108 char = u;code = 117 char = c;code = 99 char = t;code = 116 char = u;code = 117 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = t;code = 116 char = r;code = 114 char = i;code = 105 char = b;code = 98 char = u;code = 117 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = v;code = 118 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = z;code = 122 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = c;code = 99 char = u;code = 117 char = l;code = 108 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = q;code = 113 char = u;code = 117 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = b;code = 98 char = r;code = 114 char = i;code = 105 char = u;code = 117 char = m;code = 109 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = p;code = 112 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = m;code = 109 char = y;code = 121 char = l;code = 108 char = o;code = 111 char = i;code = 105 char = d;code = 100 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = m;code = 109 char = e;code = 101 char = d;code = 100 char = i;code = 105 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = .;code = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = A key pathological event in dialysis-related amyloidosis is the fibril formation of beta(2)-microglobulin (beta 2-m). Because beta 2-m does not form fibrils in vitro, except under acidic conditions, predisposing factors that may drive fibril formation at physiological pH have been the focus of much attention. One factor that may be implicated is Cu(2+) binding, which destabilizes the native state of beta 2-m and thus stabilizes the amyloid precursor. To address the Cu(2+)-induced destabilization of beta 2-m at the atomic level, we studied changes in the conformational dynamics of beta 2-m upon Cu(2+) binding. Titration of beta 2-m with Cu(2+) monitored by heteronuclear NMR showed that three out of four histidines (His13, His31, and His51) are involved in the binding at pH 7.0. (1)H-(15)N heteronuclear NOE suggested increased backbone dynamics for the residues Val49 to Ser55, implying that the Cu(2+) binding at His51 increased the local dynamics of beta-strand D. Hydrogen/deuterium exchange of amide protons showed increased flexibility of the core residues upon Cu(2+) binding. Taken together, it is likely that Cu(2+) binding increases the pico- to nanosecond fluctuation of the beta-strand D on which His51 exists, which is propagated to the core of the molecule, thus promoting the global and slow fluctuations. This may contribute to the overall destabilization of the molecule, increasing the equilibrium population of the amyloidogenic intermediate.
Publication: Protein Sci. 2004 Mar ;13(3)::797-809.
Publication Date: 2004 Mar
Study Author(s): Villanueva, James;Hoshino, Masaru;Katou, Hidenori;Kardos, József;Hasegawa, Kazuhiro;Naiki, Hironobu;Goto, Yuji;
Institution: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
Shortcut link to this study:
A key pathological event in dialysis-related amyloidosis is the fibril formation of beta(2)-microglobulin (beta 2-m). Because beta 2-m does not form fibrils in vitro, except under acidic conditions, predisposing factors that may drive fibril formation at physiological pH have been the focus of much attention. One factor that may be implicated is Cu(2+) binding, which destabilizes the native state of beta 2-m and thus stabilizes the amyloid precursor. To address the Cu(2+)-induced destabilization of beta 2-m at the atomic level, we studied changes in the conformational dynamics of beta 2-m upon Cu(2+) binding. Titration of beta 2-m with Cu(2+) monitored by heteronuclear NMR showed that three out of four histidines (His13, His31, and His51) are involved in the binding at pH 7.0. (1)H-(15)N heteronuclear NOE suggested increased backbone dynamics for the residues Val49 to Ser55, implying that the Cu(2+) binding at His51 increased the local dynamics of beta-strand D. Hydrogen/deuterium exchange of amide protons showed increased flexibility of the core residues upon Cu(2+) binding. Taken together, it is likely that Cu(2+) binding increases the pico- to nanosecond fluctuation of the beta-strand D on which His51 exists, which is propagated to the core of the molecule, thus promoting the global and slow fluctuations. This may contribute to the overall destabilization of the molecule, increasing the equilibrium population of the amyloidogenic intermediate.
PMID: 14767076