2jdf: Difference between revisions

Revision as of 19:02, 21 February 2008

HUMAN GAMMA-B CRYSTALLIN

OverviewOverview

The concept of novel binding proteins as an alternative to antibodies has undergone rapid development and is now ready for practical use in a wide range of applications. Alternative binding proteins, based on suitable scaffolds with desirable properties, are selected from combinatorial libraries in vitro. Here, we describe an approach using a beta-sheet of human gamma-B-crystallin to generate a universal binding site through randomization of eight solvent-exposed amino acid residues selected according to structural and sequence analyses. Specific variants, so-called Affilin, have been isolated from a phage display library against a variety of targets that differ considerably in size and structure. The isolated Affilin variants can be produced in Escherichia coli as soluble proteins and have a high level of thermodynamic stability. The crystal structures of the human wild-type gamma-B-crystallin and a selected Affilin variant have been determined to 1.7 A and 2.0 A resolution, respectively. Comparison of the two molecules indicates that the human gamma-B-crystallin tolerates amino acid exchanges with no major structural change. We conclude that the intrinsically stable and easily expressed gamma-B-crystallin provides a suitable framework for the generation of novel binding molecules.

About this StructureAbout this Structure

2JDF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein., Ebersbach H, Fiedler E, Scheuermann T, Fiedler M, Stubbs MT, Reimann C, Proetzel G, Rudolph R, Fiedler U, J Mol Biol. 2007 Sep 7;372(1):172-85. Epub 2007 Jun 22. PMID:17628592

Page seeded by OCA on Thu Feb 21 18:02:01 2008

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OCA

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 ==Overview==
-The concept of novel binding proteins as an alternative to antibodies has, undergone rapid development and is now ready for practical use in a wide, range of applications. Alternative binding proteins, based on suitable, scaffolds with desirable properties, are selected from combinatorial, libraries in vitro. Here, we describe an approach using a beta-sheet of, human gamma-B-crystallin to generate a universal binding site through, randomization of eight solvent-exposed amino acid residues selected, according to structural and sequence analyses. Specific variants, so-called Affilin, have been isolated from a phage display library against, a variety of targets that differ considerably in size and structure. The, isolated Affilin variants can be produced in Escherichia coli as soluble, proteins and have a high level of thermodynamic stability. The crystal, structures of the human wild-type gamma-B-crystallin and a selected, Affilin variant have been determined to 1.7 A and 2.0 A resolution, respectively. Comparison of the two molecules indicates that the human, gamma-B-crystallin tolerates amino acid exchanges with no major structural, change. We conclude that the intrinsically stable and easily expressed, gamma-B-crystallin provides a suitable framework for the generation of, novel binding molecules.
+The concept of novel binding proteins as an alternative to antibodies has undergone rapid development and is now ready for practical use in a wide range of applications. Alternative binding proteins, based on suitable scaffolds with desirable properties, are selected from combinatorial libraries in vitro. Here, we describe an approach using a beta-sheet of human gamma-B-crystallin to generate a universal binding site through randomization of eight solvent-exposed amino acid residues selected according to structural and sequence analyses. Specific variants, so-called Affilin, have been isolated from a phage display library against a variety of targets that differ considerably in size and structure. The isolated Affilin variants can be produced in Escherichia coli as soluble proteins and have a high level of thermodynamic stability. The crystal structures of the human wild-type gamma-B-crystallin and a selected Affilin variant have been determined to 1.7 A and 2.0 A resolution, respectively. Comparison of the two molecules indicates that the human gamma-B-crystallin tolerates amino acid exchanges with no major structural change. We conclude that the intrinsically stable and easily expressed gamma-B-crystallin provides a suitable framework for the generation of novel binding molecules.
 ==About this Structure==
@@ Line 10: / Line 10: @@
 ==Reference==
-Affilin-Novel Binding Molecules Based on Human gamma-B-Crystallin, an All beta-Sheet Protein., Ebersbach H, Fiedler E, Scheuermann T, Fiedler M, Stubbs MT, Reimann C, Proetzel G, Rudolph R, Fiedler U, J Mol Biol. 2007 Jun 22;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17628592 17628592]
+Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein., Ebersbach H, Fiedler E, Scheuermann T, Fiedler M, Stubbs MT, Reimann C, Proetzel G, Rudolph R, Fiedler U, J Mol Biol. 2007 Sep 7;372(1):172-85. Epub 2007 Jun 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17628592 17628592]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
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 [[Category: Rudolph, R.]]
 [[Category: Scheuermann, T.]]
-[[Category: Stubbs, M.T.]]
+[[Category: Stubbs, M T.]]
 [[Category: affilin]]
 [[Category: artificial binding protein]]
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 [[Category: structural protein]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:49:11 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:02:01 2008''