1rum: Difference between revisions

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New page: left|200px<br /> <applet load="1rum" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rum, resolution 1.48Å" /> '''Crystal structure (...
 
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[[Image:1rum.gif|left|200px]]<br />
[[Image:1rum.gif|left|200px]]<br /><applet load="1rum" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="1rum" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="1rum, resolution 1.48&Aring;" />
caption="1rum, resolution 1.48&Aring;" />
'''Crystal structure (F) of H2O2-soaked cationic cyclization antibody 4C6 fab at pH 8.5 with a data set collected at SSRL beamline 9-1.'''<br />
'''Crystal structure (F) of H2O2-soaked cationic cyclization antibody 4C6 fab at pH 8.5 with a data set collected at SSRL beamline 9-1.'''<br />


==Overview==
==Overview==
Antibodies can catalyze the generation of hydrogen peroxide (H2O2) from, singlet dioxygen (1O2*) and water via the postulated intermediacy of, dihydrogen trioxide (H2O3) and other trioxygen species. Nine different, crystal structures were determined to elucidate the chemical consequences, to the antibody molecule itself of exposure to such reactive intermediates, and to provide insights into the location on the antibody where these, species could be generated. Herein, we report structural evidence for, modifications of two specific antibody residues within the interfacial, region of the variable and constant domains of different murine antibody, antigen-binding fragments (Fabs) by reactive species generated during the, antibody-catalyzed water oxidation process. Crystal structure analyses of, murine Fabs 4C6 and 13G5 after UV-irradiation revealed complex oxidative, modifications to tryptophan L163 and, in 4C6, hydroxylation of the Cgamma, of glutamine H6. These discrete modifications of specific residues add, further support for the "active site" of the water-oxidation pathway being, located within the interfacial region of the constant and variable domains, and highlight the general resistance of the antibody molecule to oxidation, by reactive oxygen species generated during the water-oxidation process.
Antibodies can catalyze the generation of hydrogen peroxide (H2O2) from singlet dioxygen (1O2*) and water via the postulated intermediacy of dihydrogen trioxide (H2O3) and other trioxygen species. Nine different crystal structures were determined to elucidate the chemical consequences to the antibody molecule itself of exposure to such reactive intermediates and to provide insights into the location on the antibody where these species could be generated. Herein, we report structural evidence for modifications of two specific antibody residues within the interfacial region of the variable and constant domains of different murine antibody antigen-binding fragments (Fabs) by reactive species generated during the antibody-catalyzed water oxidation process. Crystal structure analyses of murine Fabs 4C6 and 13G5 after UV-irradiation revealed complex oxidative modifications to tryptophan L163 and, in 4C6, hydroxylation of the Cgamma of glutamine H6. These discrete modifications of specific residues add further support for the "active site" of the water-oxidation pathway being located within the interfacial region of the constant and variable domains and highlight the general resistance of the antibody molecule to oxidation by reactive oxygen species generated during the water-oxidation process.


==About this Structure==
==About this Structure==
1RUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with BEZ and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RUM OCA].  
1RUM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=BEZ:'>BEZ</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RUM OCA].  


==Reference==
==Reference==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Eschenmoser, A.]]
[[Category: Eschenmoser, A.]]
[[Category: Jr., P.Wentworth.]]
[[Category: Jr., P Wentworth.]]
[[Category: Lerner, R.A.]]
[[Category: Lerner, R A.]]
[[Category: Wentworth, A.D.]]
[[Category: Wentworth, A D.]]
[[Category: Wilson, I.A.]]
[[Category: Wilson, I A.]]
[[Category: Zhu, X.]]
[[Category: Zhu, X.]]
[[Category: BEZ]]
[[Category: BEZ]]
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[[Category: water oxidation]]
[[Category: water oxidation]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:41:45 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:41 2008''

Revision as of 15:54, 21 February 2008

File:1rum.gif


1rum, resolution 1.48Å

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Crystal structure (F) of H2O2-soaked cationic cyclization antibody 4C6 fab at pH 8.5 with a data set collected at SSRL beamline 9-1.

OverviewOverview

Antibodies can catalyze the generation of hydrogen peroxide (H2O2) from singlet dioxygen (1O2*) and water via the postulated intermediacy of dihydrogen trioxide (H2O3) and other trioxygen species. Nine different crystal structures were determined to elucidate the chemical consequences to the antibody molecule itself of exposure to such reactive intermediates and to provide insights into the location on the antibody where these species could be generated. Herein, we report structural evidence for modifications of two specific antibody residues within the interfacial region of the variable and constant domains of different murine antibody antigen-binding fragments (Fabs) by reactive species generated during the antibody-catalyzed water oxidation process. Crystal structure analyses of murine Fabs 4C6 and 13G5 after UV-irradiation revealed complex oxidative modifications to tryptophan L163 and, in 4C6, hydroxylation of the Cgamma of glutamine H6. These discrete modifications of specific residues add further support for the "active site" of the water-oxidation pathway being located within the interfacial region of the constant and variable domains and highlight the general resistance of the antibody molecule to oxidation by reactive oxygen species generated during the water-oxidation process.

About this StructureAbout this Structure

1RUM is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Probing the antibody-catalyzed water-oxidation pathway at atomic resolution., Zhu X, Wentworth P Jr, Wentworth AD, Eschenmoser A, Lerner RA, Wilson IA, Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2247-52. PMID:14982995

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