PDBsum entry 2cm4

Inhibitor

PDB id: 2cm4

Contents

Protein chain

145 a.a. *

Ligands

ACT

RCL

Waters ×159

* Residue conservation analysis

PDB id:

2cm4

Name:

Inhibitor

Title:

The complement inhibitor omci in complex with ricinoleic acid

Structure:

Complement inhibitor. Chain: a. Synonym: omci. Engineered: yes. Mutation: yes. Other_details: double mutation to prevent the yeast expression system to introduce glycosylation

Source:

Ornithodoros moubata. Soft tick. Organism_taxid: 6938. Expressed in: pichia methanolica. Expression_system_taxid: 33166.

Resolution:

1.90Å R-factor: 0.169 R-free: 0.210

Authors:

P.Roversi,S.Johnson,O.Lissina,G.C.Paesen,W.Boland,M.A.Nunn,S.M.Lea

Key ref:

P.Roversi et al. (2007). The structure of OMCI, a novel lipocalin inhibitor of the complement system. J Mol Biol, 369, 784-793. PubMed id: 17445829 DOI: 10.1016/j.jmb.2007.03.064

Date:

04-May-06 Release date: 01-May-07

Protein chain

Q5YD59  (C5I_ORNMO) -  Complement inhibitor from Ornithodoros moubata

Seq: 168 a.a.

Struc: 145 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2007.03.064

J Mol Biol 369:784-793 (2007)

PubMed id: 17445829

The structure of OMCI, a novel lipocalin inhibitor of the complement system.

P.Roversi, O.Lissina, S.Johnson, N.Ahmat, G.C.Paesen, K.Ploss, W.Boland, M.A.Nunn, S.M.Lea.

ABSTRACT

The complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site.

Selected figure(s)

Figure 1.
Figure 1. (a) Cartoon representations of the OmCI molecule from the P2[1]2[1]2[1]-A crystal form. Colour: blue to red, from N terminus to C terminus. The cysteine side-chains and the ricinoleic acid ligand are shown in stick representation, with C atoms coloured orange, O red and S green. The strands and helices are labelled following the tick lipocalin nomenclature.^36 (b) OmCI molecular surface coloured by electrostatic potential, in the same orientations as in (a). Contours: − 2 kT/e, red; + 2 kT/e, blue. The pictures were produced with the PyMol [http://www.pymol.sourceforge.net/]. The electrostatic potential was computed with the program APBS^42, run within PyMol, with the following parameters: ε[protein] = 2.0; ε[solvent] = 78.0; ionic strength, 150 mM NaCl. In (a) and (b), views 1 and 2 are rotated by 90° around the horizontal axis.

Figure 3.
Figure 3. (a) P2[1]2[1]2[1]-A 1.9 Å F[o]–F[c] electron density, contoured at the + 3.0 σ level, computed before any modelling of the ligand was attempted. The final model for the ricinoleic acid ligand is shown with C (orange) and O(red) surrounded by the OmCI pocket residues (C, green; O, red; N, blue; and S, yellow); the picture was produced with PyMol [http://www.pymol.sourceforge.net/]. (b) A representation of the water molecules and OmCI residues forming hydrogen bonds (with distances in Å) and non-bonding hydrophobic contacts to the ricinoleic acid. The picture was produced with the program LigPLot.^57

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 369, 784-793) copyright 2007.

Figures were selected by an automated process.