Factor IX: Difference between revisions

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Nadia Dorochko, Alexander Berchansky, David Canner, Michal Harel

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 {{STRUCTURE_1nl0|  PDB=1nl0  |  SCENE=  }}
 To further probe into the structure of FIX Gla domain, [[conformation-specific anti-Factor IX antibodies]] were utilized. Using an
-<scene name='Factor_IX/Antifactor/2'>anti-Factor IX antibody</scene>, 10C12, which is then reformatted into a F(ab')2 form (two Fab fragments connected by a leucine zipper). This antibody is a calcium specific antibody for factor IX and provides information on the inhibition of membrane binding.  by this conformation-specific antibody. The antibody interacts with the  loop (Leu-6, Phe-9, and Val-10)  of the  -carboxyglutamic acids residues bound to calcium ions in the  Gla domain.
+<scene name='Factor_IX/Antifactor/1'>anti-Factor IX antibody</scene>, 10C12, which is then reformatted into a F(ab')2 form (two Fab fragments connected by a leucine zipper). This antibody is a calcium specific antibody for factor IX and provides information on the inhibition of membrane binding.  by this conformation-specific antibody. The antibody interacts with the  loop (Leu-6, Phe-9, and Val-10)  of the  -carboxyglutamic acids residues bound to calcium ions in the  Gla domain.
-The Gla domain of Factor IX consists of an N-terminal loop and three short ''&omega;''-<scene name='Factor_IX/Antifactor_1/1'>helixes</scene>(helix A: residues 14-19; helix B: residues 24-32; helix C: residues 35-45). The calcium ions are positioned between the loop and the A and B helices with calcium liganding providing the folding energy to align the loop properly. Helices A and B are connected by a tight turn and further stabilized by a conserved disulfide bond between residues 18 and 23 of the Gla domain. The two cysteine residues also form two hydrogen bonds (Tyr-45 to Cys-18, 3.10 Å; Tyr-45 to Cys-23, 2.88 Å) to the side chain of a conserved Tyr-45 of helix C, providing an anchor to bundle three helices together. This tyrosine residue and the disulfide bond are part of the hydrophobic core between helix C and helix A/B that includes Phe-25, Ala-28, Phe-41, and Trp-42, a cluster that provides further hydrophobic energy to bind helix C to helix A/B. All of these residues are conserved among Gla domains of vitamin K-dependent proteins.
+The Gla domain of Factor IX consists of an N-terminal loop and three short ''&omega;''-<scene name='Factor_IX/Antifactor_1/2'>helixes</scene>(helix A: residues 14-19; helix B: residues 24-32; helix C: residues 35-45). The calcium ions are positioned between the loop and the A and B helices with calcium liganding providing the folding energy to align the loop properly. Helices A and B are connected by a tight turn and further stabilized by a conserved disulfide bond between residues 18 and 23 of the Gla domain. The two cysteine residues also form two hydrogen bonds (Tyr-45 to Cys-18, 3.10 Å; Tyr-45 to Cys-23, 2.88 Å) to the side chain of a conserved Tyr-45 of helix C, providing an anchor to bundle three helices together. This tyrosine residue and the disulfide bond are part of the hydrophobic core between helix C and helix A/B that includes Phe-25, Ala-28, Phe-41, and Trp-42, a cluster that provides further hydrophobic energy to bind helix C to helix A/B. All of these residues are conserved among Gla domains of vitamin K-dependent proteins.