PDBsum entry 2odq

Hydrolase

PDB id: 2odq

Contents

Protein chain

492 a.a. *

Ligands

NAG-NAG-NAG ×2

NAG ×2

Waters ×134

* Residue conservation analysis

PDB id:

2odq

Name:

Hydrolase

Title:

Complement component c2a, the catalytic fragment of c3- and c5- convertase of human complement

Structure:

Complement c2. Chain: a. Fragment: complement c2a fragment. Synonym: c3/c5 convertase. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five(bti-tn-5b1-4).

Resolution:

2.30Å R-factor: 0.217 R-free: 0.274

Authors:

S.V.L.Narayana,V.Krishnan

Key ref:

V.Krishnan et al. (2007). The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement. J Mol Biol, 367, 224-233. PubMed id: 17234210 DOI: 10.1016/j.jmb.2006.12.039

Date:

25-Dec-06 Release date: 06-Feb-07

Protein chain

Q5JP69  (Q5JP69_HUMAN) -  Complement C2 from Homo sapiens

Seq: 752 a.a.

Struc: 492 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.21.43 - classical-complement-pathway C3/C5 convertase.
• Reaction: Cleaves component C3 at the carboxyl of Arg-77 of the alpha-chain to yield C3a and C3b, and component C5 at the carboxyl of Arg-74 of the alpha-chain to yield C5a and C5b.

DOI no: 10.1016/j.jmb.2006.12.039

J Mol Biol 367:224-233 (2007)

PubMed id: 17234210

The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement.

V.Krishnan, Y.Xu, K.Macon, J.E.Volanakis, S.V.Narayana.

ABSTRACT

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.

Selected figure(s)

Figure 3.
Figure 3. (a) Overall comparison of the vWFA domain of C2a (magenta) and isolated vWFA domain of Bb (yellow). The magnesium ion of C2a is shown in silver and that of Bb is shown in pink. The N-terminal linker of C2a is shown in red and the disordered α7 helix of Bb is shown by a yellow dotted line. (b) Stereo view comparison of the α7 helix and its environment of C2a with other known integrin I-domain “open” and “closed” structures. C2 is in magenta; the ligand-free α2β1 I-domain closed form is in yellow, the ligand-bound α2β1 I-domain is in cyan and the Bb^C428–C435 mutant of Bb is in green. (c) Stereo view of superposition of the α7 helix and its environment of C2a (magenta) and Bb (yellow). The linker to the SP domain of C2a shown in blue and that to Bb is shown in green. The additional N terminus of C2a is shown in red. The sugar molecule of C2a that is located at the domain interface near the α7 helix is shown in white and labeled as NAG. The magnesium ion of C2a is shown in silver and that of Bb is shown in yellow. Figure 3. (a) Overall comparison of the vWFA domain of C2a (magenta) and isolated vWFA domain of Bb (yellow). The magnesium ion of C2a is shown in silver and that of Bb is shown in pink. The N-terminal linker of C2a is shown in red and the disordered α7 helix of Bb is shown by a yellow dotted line. (b) Stereo view comparison of the α7 helix and its environment of C2a with other known integrin I-domain “open” and “closed” structures. C2 is in magenta; the ligand-free α2β1 I-domain closed form is in yellow, the ligand-bound α2β1 I-domain is in cyan and the Bb^C428–C435 mutant of Bb is in green. (c) Stereo view of superposition of the α7 helix and its environment of C2a (magenta) and Bb (yellow). The linker to the SP domain of C2a shown in blue and that to Bb is shown in green. The additional N terminus of C2a is shown in red. The sugar molecule of C2a that is located at the domain interface near the α7 helix is shown in white and labeled as NAG. The magnesium ion of C2a is shown in silver and that of Bb is shown in yellow.

Figure 4.
Figure 4. (a) Stereo view of MIDAS motif comparison for ligand-bound and ligand-free conformations. The metal ions are shown in the same color as the main-chain ribbons, and the water molecules are in blue. The ligand-free closed conformation, in the presence of Mg^2+ for α2β1 I-domain (yellow) is superposed on the ligand-bound open conformation of α2β1 Id-main (cyan) and the ligand-free open-like conformation of C2a (magenta). A Glu residue from the ligand collagen completes the coordination of Mg in α2β1 I-domain open conformation. (b) Stereo view of a detailed comparison of the MIDAS structures of C2a (magenta) and Bb (yellow). The metal atom of C2a is shown as a silver ball and that of Bb is shown as yellow ball. Continuous thin lines indicate the metal coordination of C2a (magenta) and Bb (yellow). Water molecules are shown in blue. Figure 4. (a) Stereo view of MIDAS motif comparison for ligand-bound and ligand-free conformations. The metal ions are shown in the same color as the main-chain ribbons, and the water molecules are in blue. The ligand-free closed conformation, in the presence of Mg^2+ for α2β1 I-domain (yellow) is superposed on the ligand-bound open conformation of α2β1 Id-main (cyan) and the ligand-free open-like conformation of C2a (magenta). A Glu residue from the ligand collagen completes the coordination of Mg in α2β1 I-domain open conformation. (b) Stereo view of a detailed comparison of the MIDAS structures of C2a (magenta) and Bb (yellow). The metal atom of C2a is shown as a silver ball and that of Bb is shown as yellow ball. Continuous thin lines indicate the metal coordination of C2a (magenta) and Bb (yellow). Water molecules are shown in blue.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2007, 367, 224-233) copyright 2007.

Figures were selected by an automated process.