1llt: Difference between revisions

Line 1:

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

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

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

caption="1llt, resolution 3.10Å" />

'''BIRCH POLLEN ALLERGEN BET V 1 MUTANT E45S'''<br />

==Overview==

Specific allergy vaccination is an efficient treatment for allergic, disease; however, the development of safer vaccines would enable a more, general use of the treatment. Determination of molecular structures of, allergens and allergen-Ab complexes facilitates epitope mapping and, enables a rational approach to the engineering of allergen molecules with, reduced IgE binding. In this study, we describe the identification and, modification of a human IgE-binding epitope based on the crystal structure, of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies, approximately 10% of the molecular surface area of Bet v 1 and is clearly, conformational. A synthetic peptide representing a sequential motif in the, epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet, v 1, illustrating limitations in the use of peptides for B cell epitope, characterization. The single amino acid substitution, Glu(45)-Ser, was, introduced in the epitope and completely abolished the binding of mAb BV16, to the Bet v 1 mutant within a concentration range 1000-fold higher than, wild type. The mutant also showed up to 50% reduction in the binding of, human polyclonal IgE, demonstrating that glutamic acid 45 is a critical, amino acid also in a major human IgE-binding epitope. By solving the, three-dimensional crystal structure of the Bet v 1 Glu(45)-Ser mutant, it, was shown that the change in immunochemical activity is directly related, to the Glu(45)-Ser substitution and not to long-range structural, alterations or collapse of the Bet v 1 mutant tertiary structure.

Specific allergy vaccination is an efficient treatment for allergic disease; however, the development of safer vaccines would enable a more general use of the treatment. Determination of molecular structures of allergens and allergen-Ab complexes facilitates epitope mapping and enables a rational approach to the engineering of allergen molecules with reduced IgE binding. In this study, we describe the identification and modification of a human IgE-binding epitope based on the crystal structure of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies approximately 10% of the molecular surface area of Bet v 1 and is clearly conformational. A synthetic peptide representing a sequential motif in the epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet v 1, illustrating limitations in the use of peptides for B cell epitope characterization. The single amino acid substitution, Glu(45)-Ser, was introduced in the epitope and completely abolished the binding of mAb BV16 to the Bet v 1 mutant within a concentration range 1000-fold higher than wild type. The mutant also showed up to 50% reduction in the binding of human polyclonal IgE, demonstrating that glutamic acid 45 is a critical amino acid also in a major human IgE-binding epitope. By solving the three-dimensional crystal structure of the Bet v 1 Glu(45)-Ser mutant, it was shown that the change in immunochemical activity is directly related to the Glu(45)-Ser substitution and not to long-range structural alterations or collapse of the Bet v 1 mutant tertiary structure.

==About this Structure==

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

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

==Reference==

Line 16:

Line 15:

[[Category: Gajhede, M.]]

[[Category: Ipsen, H.]]

[[Category: Larsen, J.N.]]

[[Category: Larsen, J N.]]

[[Category: Mirza, O.]]

[[Category: Neerven, R.J.Van.]]

[[Category: Neerven, R J.Van.]]

[[Category: Spangfort, M.D.]]

[[Category: Spangfort, M D.]]

[[Category: allergen]]

[[Category: pathogenesis related proteins]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Sun Nov 18 09~~:35:~~37 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:46:07 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:1llt.gif|left|200px]]<br />
+[[Image:1llt.gif|left|200px]]<br /><applet load="1llt" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1llt" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1llt, resolution 3.10&Aring;" />
 '''BIRCH POLLEN ALLERGEN BET V 1 MUTANT E45S'''<br />
 ==Overview==
-Specific allergy vaccination is an efficient treatment for allergic, disease; however, the development of safer vaccines would enable a more, general use of the treatment. Determination of molecular structures of, allergens and allergen-Ab complexes facilitates epitope mapping and, enables a rational approach to the engineering of allergen molecules with, reduced IgE binding. In this study, we describe the identification and, modification of a human IgE-binding epitope based on the crystal structure, of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies, approximately 10% of the molecular surface area of Bet v 1 and is clearly, conformational. A synthetic peptide representing a sequential motif in the, epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet, v 1, illustrating limitations in the use of peptides for B cell epitope, characterization. The single amino acid substitution, Glu(45)-Ser, was, introduced in the epitope and completely abolished the binding of mAb BV16, to the Bet v 1 mutant within a concentration range 1000-fold higher than, wild type. The mutant also showed up to 50% reduction in the binding of, human polyclonal IgE, demonstrating that glutamic acid 45 is a critical, amino acid also in a major human IgE-binding epitope. By solving the, three-dimensional crystal structure of the Bet v 1 Glu(45)-Ser mutant, it, was shown that the change in immunochemical activity is directly related, to the Glu(45)-Ser substitution and not to long-range structural, alterations or collapse of the Bet v 1 mutant tertiary structure.
+Specific allergy vaccination is an efficient treatment for allergic disease; however, the development of safer vaccines would enable a more general use of the treatment. Determination of molecular structures of allergens and allergen-Ab complexes facilitates epitope mapping and enables a rational approach to the engineering of allergen molecules with reduced IgE binding. In this study, we describe the identification and modification of a human IgE-binding epitope based on the crystal structure of Bet v 1 in complex with the BV16 Fab' fragment. The epitope occupies approximately 10% of the molecular surface area of Bet v 1 and is clearly conformational. A synthetic peptide representing a sequential motif in the epitope (11 of 16 residues) did not inhibit the binding of mAb BV16 to Bet v 1, illustrating limitations in the use of peptides for B cell epitope characterization. The single amino acid substitution, Glu(45)-Ser, was introduced in the epitope and completely abolished the binding of mAb BV16 to the Bet v 1 mutant within a concentration range 1000-fold higher than wild type. The mutant also showed up to 50% reduction in the binding of human polyclonal IgE, demonstrating that glutamic acid 45 is a critical amino acid also in a major human IgE-binding epitope. By solving the three-dimensional crystal structure of the Bet v 1 Glu(45)-Ser mutant, it was shown that the change in immunochemical activity is directly related to the Glu(45)-Ser substitution and not to long-range structural alterations or collapse of the Bet v 1 mutant tertiary structure.
 ==About this Structure==
-LLT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Betula_pendula Betula pendula]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LLT OCA].
+LLT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Betula_pendula Betula pendula]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LLT OCA].
 ==Reference==
@@ Line 16: / Line 15: @@
 [[Category: Gajhede, M.]]
 [[Category: Ipsen, H.]]
-[[Category: Larsen, J.N.]]
+[[Category: Larsen, J N.]]
 [[Category: Mirza, O.]]
-[[Category: Neerven, R.J.Van.]]
+[[Category: Neerven, R J.Van.]]
-[[Category: Spangfort, M.D.]]
+[[Category: Spangfort, M D.]]
 [[Category: allergen]]
 [[Category: pathogenesis related proteins]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:35:37 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:46:07 2008''