PDBsum entry: 1xkg

Hydrolase

PDB id: 1xkg

Contents

Protein chain

298 a.a. *

Ligands

SO4 ×2

GOL ×2

Metals

YT3

Waters ×312

* Residue conservation analysis

PDB id:

1xkg

Name:

Hydrolase

Title:

Crystal structure of the major house dust mite allergen der pro form at 1.61 a resolution

Structure:

Major mite fecal allergen der p 1. Chain: a. Fragment: residues 19-320. Synonym: der p i. Engineered: yes. Mutation: yes

Source:

Dermatophagoides pteronyssinus. European house dust mite. Organism_taxid: 6956. Gene: derp1. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Resolution:

1.61Å R-factor: 0.154 R-free: 0.186

Authors:

K.Meno,P.B.Thorsted,M.Gajhede

Key ref:

K.Meno et al. (2005). The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen. J Immunol, 175, 3835-3845. PubMed id: 16148130 Ref: Full text

Date:

29-Sep-04 Release date: 28-Jun-05

Protein chain

P08176  (PEPT1_DERPT) -  Peptidase 1

Seq: 320 a.a.

Struc: 298 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

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

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biological process: proteolysis (1 term)
• Biochemical function: hydrolase activity (4 terms)

Full text	J Immunol 175:3835-3845 (2005)
PubMed id: 16148130

The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen.

K.Meno, P.B.Thorsted, H.Ipsen, O.Kristensen, J.N.Larsen, M.D.Spangfort, M.Gajhede, K.Lund.

ABSTRACT

Allergy to house dust mite is among the most prevalent allergic diseases worldwide. Most house dust mite allergic patients react to Der p 1 from Dermatophagoides pteronyssinus, which is a cysteine protease. To avoid heterogeneity in the sample used for crystallization, a modified recombinant molecule was produced. The sequence of the proDer p 1 allergen was modified to reduce glycosylation and to abolish enzymatic activity. The resulting rproDer p 1 preparation was homogenous and stable and yielded crystals diffracting to a resolution of 1.61 A. The active site is located in a large cleft on the surface of the molecule. The 80-aa pro-peptide adopts a unique fold that interacts with the active site cleft and a substantial adjacent area on the mature region, excluding access to the cleft and the active site. Studies performed using crossed-line immunoelectrophoresis and IgE inhibition experiments indicated that several epitopes are covered by the pro-peptide and that the epitopes on the recombinant mature molecule are indistinguishable from those on the natural one. The structure confirms previous results suggesting a preference for aliphatic residues in the important P2 position in substrates. Sequence variations in related species are concentrated on the surface, which explains the existence of cross-reacting and species-specific antibodies. This study describes the first crystal structure of one of the clinically most important house dust mite allergens, the cysteine protease Der p 1.