The Role of Proteolytically Inactive Serine Proteases from Sarcoptes scabiei in Complement Evasion - Proteinases as Drug Targets - page 100

dust mite homologs, 33 distinct contigs were identified with the closest BlastX
matches to the group 3 house dust mite allergens Der p 3, Der f 3, and Eur m 3
(Figure 4.2A). 53
House dust mite group 3 allergens are serine proteases of the S1 family and
are related to chymotrypsin and trypsin. They are secreted into the mite gut
and, when excreted in the fecal pellet, 54 become aerosols that can cause
asthma. 55 The scabies mite sequence with the closest BlastX match to Der p 3
was designated Sar s 3. It resembles the group 3 allergens, as it contains six
cysteine residues involved in three disulfide bonds, an intact catalytic triad with
histidine at position 46, aspartic acid at position 93, serine at position 202, and

Figure 4.2

(A) Phylogenetic tree illustrating the inferred evolutionary relationships
between the SMIPP-Ss generated in MEGA4, 132 with maximum like-
lihood branch lengths inferred using the WAG amino acid matrix in
PAML4.1. 133 SMIPP-Ss are shown in black, Sar s 3, Der p 3 and out-
groups in gray. The tree is rooted at the vertebrate-arthropod divergence.
On the right-hand side of each clade, mutations of the catalytic triad
residues for that clade are shown as horizontal triplets, corresponding with
the H63, D107, and S200 positions, respectively (human trypsin num-
bering). Outgroup sequences are D. pteronyssinus Der p 3 (accession
DERP3_DERPT), D. melanogaster gamma trypsin (TRYG_DROME),
H. sapiens trypsin 2 (TRY2_HUMAN), and D. rerio trypsin (NP_571783).
Figure adapted and simplified from Fischer et al. 59 (B) Schematic dia-
grams of the major structural elements of selected proteins highlighted in
(A). The following code applies: The signal peptide is shown as a box with
horizontal lines, the propeptide as a box with vertical lines and the mature
protein as a white box. Predicted N-glycosylation sites are indicated as
boxes in light gray, the catalytic triad as a black box, disulfide bonds (SS)
as loops and the conserved amino acid 200 as a box in dark gray.