2odq
From Proteopedia
(New page: 200px<br /> <applet load="2odq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2odq, resolution 2.30Å" /> '''Complement componen...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2odq.gif|left|200px]]<br /> | + | [[Image:2odq.gif|left|200px]]<br /><applet load="2odq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2odq" size=" | + | |
caption="2odq, resolution 2.30Å" /> | caption="2odq, resolution 2.30Å" /> | ||
'''Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement'''<br /> | '''Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The multi-domain serine protease C2 provides the catalytic activity for | + | The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)-dependent binding of C2 to C4b, and the subsequent cleavage of C2 by C1s or MASP2, respectively. The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. Although the overall domain arrangement of C2a is similar to Bb, there are certain structural differences. Unexpectedly, the conformation of the metal ion-dependent adhesion site and the position of the alpha7 helix of the vWFA domain indicate a co-factor-bound or open conformation. The active site of the SP domain is in a zymogen-like inactive conformation. On the basis of these structural features, we suggest a model for the initial steps of C3 convertase assembly. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2ODQ 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 NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Classical-complement-pathway_C3/C5_convertase Classical-complement-pathway C3/C5 convertase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.43 3.4.21.43] Full crystallographic information is available from [http:// | + | 2ODQ 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=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Classical-complement-pathway_C3/C5_convertase Classical-complement-pathway C3/C5 convertase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.43 3.4.21.43] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ODQ OCA]. |
==Reference== | ==Reference== | ||
| - | The crystal structure of | + | The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement., Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV, J Mol Biol. 2007 Mar 16;367(1):224-33. Epub 2006 Dec 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17234210 17234210] |
[[Category: Classical-complement-pathway C3/C5 convertase]] | [[Category: Classical-complement-pathway C3/C5 convertase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Krishnan, V.]] | [[Category: Krishnan, V.]] | ||
| - | [[Category: Narayana, S | + | [[Category: Narayana, S V.L.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: c3/c5 convertase]] | [[Category: c3/c5 convertase]] | ||
| Line 29: | Line 28: | ||
[[Category: vwfa]] | [[Category: vwfa]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:17:18 2008'' |
Revision as of 16:17, 21 February 2008
|
Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement
Contents |
Overview
The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)-dependent binding of C2 to C4b, and the subsequent cleavage of C2 by C1s or MASP2, respectively. The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. Although the overall domain arrangement of C2a is similar to Bb, there are certain structural differences. Unexpectedly, the conformation of the metal ion-dependent adhesion site and the position of the alpha7 helix of the vWFA domain indicate a co-factor-bound or open conformation. The active site of the SP domain is in a zymogen-like inactive conformation. On the basis of these structural features, we suggest a model for the initial steps of C3 convertase assembly.
Disease
Known diseases associated with this structure: C2 deficiency OMIM:[217000], Macular degeneration, age-related, reduced risk of OMIM:[217000]
About this Structure
2ODQ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Classical-complement-pathway C3/C5 convertase, with EC number 3.4.21.43 Full crystallographic information is available from OCA.
Reference
The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement., Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV, J Mol Biol. 2007 Mar 16;367(1):224-33. Epub 2006 Dec 19. PMID:17234210
Page seeded by OCA on Thu Feb 21 18:17:18 2008
