1jps: Difference between revisions

Line 1:

[[Image:1jps.gif|left|200px]]<br />

[[Image:1jps.gif|left|200px]]<br /><applet load="1jps" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1jps" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1jps, resolution 1.85Å" />

'''Crystal structure of tissue factor in complex with humanized Fab D3h44'''<br />

==Overview==

The outstanding importance of the antigen-antibody recognition process for, the survival and defence strategy of higher organisms is in sharp contrast, to the limited high resolution structural data available on, antibody-antigen pairs with antigenic proteins. The limitation is the most, severe for structural data not restricted to the antigen-antibody complex, but extending to the uncomplexed antigen and antibody. We report the, crystal structure of the complex between tissue factor (TF) and the, humanized Fab fragment D3h44 at a resolution of 1.85 A together with the, structure of uncomplexed D3h44 at the same resolution. In conjunction with, the previously reported 1.7 A crystal structure of uncomplexed TF, a, unique opportunity is generated to explore details of the recognition, process. The TF.D3h44 interface is characterised by a high number of polar, interactions, including as may as 46 solvent molecules. Conformational, changes upon complex formation are very small and almost exclusively, limited to the reorientation of side-chains. The binding epitope is in, complete agreement with earlier mutagenesis experiments. A revaluation of, two other antibody-antigen pairs reported at similar resolutions, shows, that all these complexes are very similar with respect to the solvation of, the interface, the number of solvent positions conserved in the, uncomplexed and complexed proteins and the number of water molecules, expelled from the surface and replaced by hydrophilic atoms from the, binding partner upon complex formation. A strategy is proposed on how to, exploit this high resolution structural data to guide the affinity, maturation of humanised antibodies.

The outstanding importance of the antigen-antibody recognition process for the survival and defence strategy of higher organisms is in sharp contrast to the limited high resolution structural data available on antibody-antigen pairs with antigenic proteins. The limitation is the most severe for structural data not restricted to the antigen-antibody complex but extending to the uncomplexed antigen and antibody. We report the crystal structure of the complex between tissue factor (TF) and the humanized Fab fragment D3h44 at a resolution of 1.85 A together with the structure of uncomplexed D3h44 at the same resolution. In conjunction with the previously reported 1.7 A crystal structure of uncomplexed TF, a unique opportunity is generated to explore details of the recognition process. The TF.D3h44 interface is characterised by a high number of polar interactions, including as may as 46 solvent molecules. Conformational changes upon complex formation are very small and almost exclusively limited to the reorientation of side-chains. The binding epitope is in complete agreement with earlier mutagenesis experiments. A revaluation of two other antibody-antigen pairs reported at similar resolutions, shows that all these complexes are very similar with respect to the solvation of the interface, the number of solvent positions conserved in the uncomplexed and complexed proteins and the number of water molecules expelled from the surface and replaced by hydrophilic atoms from the binding partner upon complex formation. A strategy is proposed on how to exploit this high resolution structural data to guide the affinity maturation of humanised antibodies.

==Disease==

Line 11:

Line 10:

==About this Structure==

1JPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1JPS OCA].

1JPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JPS OCA].

==Reference==

Line 18:

Line 17:

[[Category: Single protein]]

[[Category: Faelber, K.]]

[[Category: Kelley, R.F.]]

[[Category: Kelley, R F.]]

[[Category: Kirchhofer, D.]]

[[Category: Muller, Y.A.]]

[[Category: Muller, Y A.]]

[[Category: Presta, L.]]

[[Category: antigen-antibody recognition]]

Line 28:

Line 27:

[[Category: interface water molecules]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 17~~:43:~~20 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:25:24 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:1jps.gif|left|200px]]<br />
+[[Image:1jps.gif|left|200px]]<br /><applet load="1jps" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1jps" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1jps, resolution 1.85&Aring;" />
 '''Crystal structure of tissue factor in complex with humanized Fab D3h44'''<br />
 ==Overview==
-The outstanding importance of the antigen-antibody recognition process for, the survival and defence strategy of higher organisms is in sharp contrast, to the limited high resolution structural data available on, antibody-antigen pairs with antigenic proteins. The limitation is the most, severe for structural data not restricted to the antigen-antibody complex, but extending to the uncomplexed antigen and antibody. We report the, crystal structure of the complex between tissue factor (TF) and the, humanized Fab fragment D3h44 at a resolution of 1.85 A together with the, structure of uncomplexed D3h44 at the same resolution. In conjunction with, the previously reported 1.7 A crystal structure of uncomplexed TF, a, unique opportunity is generated to explore details of the recognition, process. The TF.D3h44 interface is characterised by a high number of polar, interactions, including as may as 46 solvent molecules. Conformational, changes upon complex formation are very small and almost exclusively, limited to the reorientation of side-chains. The binding epitope is in, complete agreement with earlier mutagenesis experiments. A revaluation of, two other antibody-antigen pairs reported at similar resolutions, shows, that all these complexes are very similar with respect to the solvation of, the interface, the number of solvent positions conserved in the, uncomplexed and complexed proteins and the number of water molecules, expelled from the surface and replaced by hydrophilic atoms from the, binding partner upon complex formation. A strategy is proposed on how to, exploit this high resolution structural data to guide the affinity, maturation of humanised antibodies.
+The outstanding importance of the antigen-antibody recognition process for the survival and defence strategy of higher organisms is in sharp contrast to the limited high resolution structural data available on antibody-antigen pairs with antigenic proteins. The limitation is the most severe for structural data not restricted to the antigen-antibody complex but extending to the uncomplexed antigen and antibody. We report the crystal structure of the complex between tissue factor (TF) and the humanized Fab fragment D3h44 at a resolution of 1.85 A together with the structure of uncomplexed D3h44 at the same resolution. In conjunction with the previously reported 1.7 A crystal structure of uncomplexed TF, a unique opportunity is generated to explore details of the recognition process. The TF.D3h44 interface is characterised by a high number of polar interactions, including as may as 46 solvent molecules. Conformational changes upon complex formation are very small and almost exclusively limited to the reorientation of side-chains. The binding epitope is in complete agreement with earlier mutagenesis experiments. A revaluation of two other antibody-antigen pairs reported at similar resolutions, shows that all these complexes are very similar with respect to the solvation of the interface, the number of solvent positions conserved in the uncomplexed and complexed proteins and the number of water molecules expelled from the surface and replaced by hydrophilic atoms from the binding partner upon complex formation. A strategy is proposed on how to exploit this high resolution structural data to guide the affinity maturation of humanised antibodies.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-JPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JPS OCA].
+JPS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JPS OCA].
 ==Reference==
@@ Line 18: / Line 17: @@
 [[Category: Single protein]]
 [[Category: Faelber, K.]]
-[[Category: Kelley, R.F.]]
+[[Category: Kelley, R F.]]
 [[Category: Kirchhofer, D.]]
-[[Category: Muller, Y.A.]]
+[[Category: Muller, Y A.]]
 [[Category: Presta, L.]]
 [[Category: antigen-antibody recognition]]
@@ Line 28: / Line 27: @@
 [[Category: interface water molecules]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:43:20 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:25:24 2008''