1rs0
From Proteopedia
(New page: 200px<br /> <applet load="1rs0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rs0, resolution 2.60Å" /> '''Crystal Structure A...) |
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| - | [[Image:1rs0.gif|left|200px]]<br /> | + | [[Image:1rs0.gif|left|200px]]<br /><applet load="1rs0" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1rs0" size=" | + | |
caption="1rs0, resolution 2.60Å" /> | caption="1rs0, resolution 2.60Å" /> | ||
'''Crystal Structure Analysis of the Bb segment of Factor B complexed with Di-isopropyl-phosphate (DIP)'''<br /> | '''Crystal Structure Analysis of the Bb segment of Factor B complexed with Di-isopropyl-phosphate (DIP)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The C-terminal fragment, Bb, of factor B combines with C3b to form the | + | The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1RS0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with IOD, NA, MG and DFP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alternative-complement-pathway_C3/C5_convertase Alternative-complement-pathway C3/C5 convertase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.47 3.4.21.47] Full crystallographic information is available from [http:// | + | 1RS0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=IOD:'>IOD</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=DFP:'>DFP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alternative-complement-pathway_C3/C5_convertase Alternative-complement-pathway C3/C5 convertase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.47 3.4.21.47] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RS0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Macon, K.]] | [[Category: Macon, K.]] | ||
[[Category: Moore, D.]] | [[Category: Moore, D.]] | ||
| - | [[Category: Narayana, S | + | [[Category: Narayana, S V.]] |
[[Category: Ponnuraj, K.]] | [[Category: Ponnuraj, K.]] | ||
| - | [[Category: Volanakis, J | + | [[Category: Volanakis, J E.]] |
[[Category: Xu, Y.]] | [[Category: Xu, Y.]] | ||
[[Category: DFP]] | [[Category: DFP]] | ||
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[[Category: factor bb-dip complex]] | [[Category: factor bb-dip complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:13 2008'' |
Revision as of 12:54, 21 February 2008
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Crystal Structure Analysis of the Bb segment of Factor B complexed with Di-isopropyl-phosphate (DIP)
Contents |
Overview
The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation.
Disease
Known diseases associated with this structure: Macular degeneration, age-related, reduced risk of OMIM:[138470]
About this Structure
1RS0 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Alternative-complement-pathway C3/C5 convertase, with EC number 3.4.21.47 Full crystallographic information is available from OCA.
Reference
Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase., Ponnuraj K, Xu Y, Macon K, Moore D, Volanakis JE, Narayana SV, Mol Cell. 2004 Apr 9;14(1):17-28. PMID:15068800
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