PDBsum entry 1md7

Hydrolase

PDB id: 1md7

Contents

Protein chain

304 a.a. *

Ligands

NAG

Waters ×117

* Residue conservation analysis

PDB id:

1md7

Name:

Hydrolase

Title:

Monomeric structure of the zymogen of complement protease c1r

Structure:

C1r complement serine protease. Chain: a. Fragment: c-terminal ccp-sp domain. Synonym: complement c1r component. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high fivetm.

Resolution:

3.20Å R-factor: 0.217 R-free: 0.285

Authors:

M.Budayova-Spano,W.Grabarse,N.M.Thielens,H.Hillen,M.Lacroix, M.Schmidt,J.Fontecilla-Camps,G.J.Arlaud,C.Gaboriaud

Key ref:

M.Budayova-Spano et al. (2002). Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism. Structure, 10, 1509-1519. PubMed id: 12429092 DOI: 10.1016/S0969-2126(02)00881-X

Date:

07-Aug-02 Release date: 07-Aug-03

Protein chain

P00736  (C1R_HUMAN) -  Complement C1r subcomponent from Homo sapiens

Seq: 705 a.a.

Struc: 304 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.4.21.41 - complement subcomponent C1r.
• Reaction: Selective cleavage of Lys(or Arg)-|-Ile bond in complement subcomponent C1s to form the active form of C1s (EC 3.4.21.42).

DOI no: 10.1016/S0969-2126(02)00881-X

Structure 10:1509-1519 (2002)

PubMed id: 12429092

Monomeric structures of the zymogen and active catalytic domain of complement protease c1r: further insights into the c1 activation mechanism.

M.Budayova-Spano, W.Grabarse, N.M.Thielens, H.Hillen, M.Lacroix, M.Schmidt, J.C.Fontecilla-Camps, G.J.Arlaud, C.Gaboriaud.

ABSTRACT

C1r is the serine protease (SP) that mediates autoactivation of C1, the complex that triggers the classical complement pathway. We have determined the crystal structure of two fragments from the human C1r catalytic domain, each encompassing the second complement control protein (CCP2) module and the SP domain. The wild-type species has an active structure, whereas the S637A mutant is a zymogen. The structures reveal a restricted hinge flexibility of the CCP2-SP interface, and both are characterized by the unique alpha-helical conformation of loop E. The zymogen activation domain exhibits high mobility, and the active structure shows a restricted access to most substrate binding subsites. Further implications relevant to the C1r self-activation process are derived from protein-protein interactions in the crystals.

Selected figure(s)

Figure 1.
Figure 1. Overall Structures of the C1r CCP2-SP AssembliesThe WT, S637A, and R446Q molecules are shown in green, red, and cyan, respectively. The structure shown for R446Q is that of molecule B of the R446Q dimer [17].(A) Superimposition of the S637A and WT structures (stereo view). Loops are labeled according to Perona and Craik [19]. a.s., active site.(B) Superposition of the assemblies on the CCP2 module structures (partial view), illustrating the divergent orientations of the polypeptide chain in the SP domains.(C) Detailed view of the hinge region in the three structures. Residues Pro432, Val433, Cys434, and Cys560 are shown as balls and sticks.

The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1509-1519) copyright 2002.

Figure was selected by an automated process.