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result sql = Structural analysis of farnesyl pyrophosphate synthase from parasitic protozoa, a potential chemotherapeutic target.
Structural analysis of farnesyl pyrophosphate synthase from parasitic protozoa, a potential chemotherapeutic target.
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char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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 = d;code = 100
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = O;code = 79
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 = t;code = 116
char = o;code = 111
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
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 = p;code = 112
char = h;code = 104
char = y;code = 121
char = l;code = 108
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 = t;code = 116
char = r;code = 114
char = e;code = 101
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = u;code = 117
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
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 = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = F;code = 70
char = P;code = 80
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = F;code = 70
char = P;code = 80
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = z;code = 122
char = o;code = 111
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = t;code = 116
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
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 = 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 = i;code = 105
char = s;code = 115
char = o;code = 111
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = t;code = 116
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 = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = o;code = 111
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 = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = y;code = 121
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 = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = F;code = 70
char = P;code = 80
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
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 = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = B;code = 66
char = X;code = 88
char = B;code = 66
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = f;code = 102
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = x;code = 120
char = ;code = 32
char = J;code = 74
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = V;code = 86
char = a;code = 97
char = r;code = 114
char = i;code = 105
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 = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
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 = ;code = 32
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = s;code = 115
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 = f;code = 102
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = f;code = 102
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = m;code = 109
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 = F;code = 70
char = A;code = 65
char = R;code = 82
char = M;code = 77
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 = p;code = 112
char = l;code = 108
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
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 = c;code = 99
char = h;code = 104
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = t;code = 116
char = h;code = 104
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 = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = y;code = 121
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
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 = i;code = 105
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = z;code = 122
char = o;code = 111
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = F;code = 70
char = P;code = 80
char = P;code = 80
char = S;code = 83
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = z;code = 122
char = o;code = 111
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = F;code = 70
char = P;code = 80
char = P;code = 80
char = S;code = 83
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 = u;code = 117
char = s;code = 115
char = e;code = 101
char = f;code = 102
char = u;code = 117
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = F;code = 70
char = P;code = 80
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = o;code = 111
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = z;code = 122
char = o;code = 111
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Synthesis of farnesyl pyrophosphate (FPP), a key intermediate of the isoprenoid biosynthesis pathway, is catalyzed by FPP synthase (FPPS). Antiprotozoal properties of bisphosphonates, which target FPPS, have generated interest in FPPS as a potential antiprotozoal drug target. The genes encoding FPPS from parasitic protozoa were assessed to analyze structural and functional features of the enzyme. Comparisons of the FPPS from the parasitic protozoa and search for conserved motifs revealed that FPPS from both apicomplexan and trypanosomatid parasites show characteristic conserved regions for example first aspartate rich motif (FARM) contained within II conserved domain and the second aspartate rich motif (SARM) contained within VI conserved domain. Phylogenetic analysis of FPPS generated a tree with three distinct clusters. Overall topology of the phylogenic tree constructed with small subunit ribosomal RNA sequences was almost similar to that constructed with FPPS sequences. Comparative homology modeling and structural comparisons of FPPS from the parasitic protozoa provided significant insights into common and distinct characteristics of the enzyme. The critical interacting residues of the isopentenyl pyrophosphate binding site are conserved across the enzymes from the family except for malarial FPPS where the C-terminal residues from the BXB motif of helix J were missing. Variations noticed in aromatic residue pairs at the fourth and fifth position upstream of the FARM, which play important role in determination of chain length of the polyprenyl products, may produce functional differences among protozoan FPPSs. The structural comparison of protozoan FPPS may be useful in designing common or selective FPPS inhibitors as potential broad spectrum or selective antiprotozoal agents.

Publication: Infect Disord Drug Targets 2008 Mar ;8(1)::16-30.
Publication Date: 2008 Mar
Study Author(s): Srivastava, Anuradha;Mukherjee, Prasenjit;Desai, Prashant V;Avery, Mitchell A;Tekwani, Babu L;
Institution: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
Shortcut link to this study:
Synthesis of farnesyl pyrophosphate (FPP), a key intermediate of the isoprenoid biosynthesis pathway, is catalyzed by FPP synthase (FPPS). Antiprotozoal properties of bisphosphonates, which target FPPS, have generated interest in FPPS as a potential antiprotozoal drug target. The genes encoding FPPS from parasitic protozoa were assessed to analyze structural and functional features of the enzyme. Comparisons of the FPPS from the parasitic protozoa and search for conserved motifs revealed that FPPS from both apicomplexan and trypanosomatid parasites show characteristic conserved regions for example first aspartate rich motif (FARM) contained within II conserved domain and the second aspartate rich motif (SARM) contained within VI conserved domain. Phylogenetic analysis of FPPS generated a tree with three distinct clusters. Overall topology of the phylogenic tree constructed with small subunit ribosomal RNA sequences was almost similar to that constructed with FPPS sequences. Comparative homology modeling and structural comparisons of FPPS from the parasitic protozoa provided significant insights into common and distinct characteristics of the enzyme. The critical interacting residues of the isopentenyl pyrophosphate binding site are conserved across the enzymes from the family except for malarial FPPS where the C-terminal residues from the BXB motif of helix J were missing. Variations noticed in aromatic residue pairs at the fourth and fifth position upstream of the FARM, which play important role in determination of chain length of the polyprenyl products, may produce functional differences among protozoan FPPSs. The structural comparison of protozoan FPPS may be useful in designing common or selective FPPS inhibitors as potential broad spectrum or selective antiprotozoal agents.
PMID: 18473904

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