PDBsum entry 5vpk

Hydrolase

PDB id: 5vpk

Contents

Protein chains

223 a.a.

Ligands

SO4 ×6

NAG ×2

Waters ×289

PDB id:

5vpk

Name:

Hydrolase

Title:

Crystal structure of mite allergen der f 1

Structure:

Der f 1 variant. Chain: a, b, c. Fragment: sequence database residues 99-321

Source:

Dermatophagoides farinae. American house dust mite. Organism_taxid: 6954

Resolution:

2.00Å R-factor: 0.181 R-free: 0.210

Authors:

M.Chruszcz,M.D.Chapman,L.D.Vailes,A.Pomes,W.Minor

Key ref:

M.Chruszcz et al. (2009). Crystal structures of mite allergens Der f 1 and Der p 1 reveal differences in surface-exposed residues that may influence antibody binding. J Mol Biol, 386, 520-530. PubMed id: 19136006 DOI: 10.1016/j.jmb.2008.12.049

Date:

05-May-17 Release date: 24-May-17

Supersedes:

3d6s

Protein chains

P16311  (PEPT1_DERFA) -  Peptidase 1 from Dermatophagoides farinae

Seq: 321 a.a.

Struc: 223 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.4.22.65 - peptidase 1 (mite).

DOI no: 10.1016/j.jmb.2008.12.049

J Mol Biol 386:520-530 (2009)

PubMed id: 19136006

Crystal structures of mite allergens Der f 1 and Der p 1 reveal differences in surface-exposed residues that may influence antibody binding.

M.Chruszcz, M.D.Chapman, L.D.Vailes, E.A.Stura, J.M.Saint-Remy, W.Minor, A.Pomés.

ABSTRACT

The group 1 mite allergens Der f 1 and Der p 1 are potent allergens excreted by Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively. The human immunoglobulin E antibody responses to the group 1 allergens show more cross-reactivity than the murine immunoglobulin G antibody responses, which are largely species specific. Here, we report the crystal structure of the mature form of Der f 1, which was isolated from its natural source, and a new high-resolution structure of mature recombinant Der p 1. Unlike Der p 1, Der f 1 is monomeric both in the crystalline state and in solution. Moreover, no metal binding is observed in the structure of Der f 1 despite the fact that all amino acids involved in Ca(2+) binding in Der p 1 are completely conserved in Der f 1. Although Der p 1 and Der f 1 share an extensive sequence identity, comparison of the crystal structures of both allergens revealed structural features that could explain the differences in murine IgG and human IgE antibody responses to these allergens. There are structural differences between Der f 1 and Der p 1 that are unevenly distributed on the allergens' surfaces. This uneven spatial arrangement of conserved versus altered residues could explain both the specificity and cross-reactivity of antibodies against Der f 1 and Der p 1.

Selected figure(s)

Figure 2.
Fig. 2. (a) Superposition of the Der f 1 (green) and Der p 1 (yellow) active sites. Interactions between residues are marked with dashed lines, and interatomic distances (see Table 1) are in Å. (b) Superposition of the putative Der f 1 metal binding site (green) with the metal binding site observed in the proDer p 1 (blue; PDB code 1XKG) and mature Der p 1 (yellow) structures. Residues are numbered according to the Der f 1 sequence. The water molecules coordinating Y^3+ (cyan sphere) were omitted for the sake of picture clarity. Coordination of Ca^2+ (black sphere) in the Der p 1 structure (PDB code 3F5V) is shown using dashed lines. (c) Water molecules (red spheres) conserved in the Der f 1 (PDB code 3D6S), proDer p 1 (PDB code 1XKG) and mature Der p 1 (PDB code 3F5V) crystal structures. Black sphere shows the position of the metal ion in the structure of Der p 1.

Figure 3.
Fig. 3. (a) The putative dimer formed by mature Der p 1 (PDB codes 2AS8 and 3F5V). Der p 1 molecules are shown in ribbon representation, while calcium ions are shown as red spheres. (b) Tyr166 and Gln167 (Der f 1 numbering) are blocking the catalytic cleft in a putative dimer of Der p 1. Chain A is shown in surface representation (green); chain B is shown in blue, while catalytic Cys35A is shown in orange.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 386, 520-530) copyright 2009.

Figures were selected by an automated process.