PDBsum entry 2uuy

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
223 a.a. *
52 a.a. *
Waters ×510
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of a tick tryptase inhibitor in complex with bovine trypsin
Structure: Cationic trypsin. Chain: a. Fragment: residues 21-243. Synonym: trypsin from bovine pancreas, beta-trypsin. Tryptase inhibitor. Chain: b. Fragment: residues 45-96. Synonym: tryptase inhibitor tdpi
Source: Bos taurus. Bovine. Organism_taxid: 9913. Tissue: pancreas. Rhipicephalus appendiculatus. Brown ear tick. Organism_taxid: 34631
1.15Å     R-factor:   0.132     R-free:   0.163
Authors: C.Siebold,G.C.Paesen,K.Harlos,M.F.Peacey,P.A.Nuttall, D.I.Stuart
Key ref:
G.C.Paesen et al. (2007). A tick protein with a modified Kunitz fold inhibits human tryptase. J Mol Biol, 368, 1172-1186. PubMed id: 17391695 DOI: 10.1016/j.jmb.2007.03.011
08-Mar-07     Release date:   10-Apr-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00760  (TRY1_BOVIN) -  Cationic trypsin
246 a.a.
223 a.a.
Protein chain
Q1EG59  (Q1EG59_RHIAP) -  Tryptase inhibitor
118 a.a.
52 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.  - Trypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     digestion   2 terms 
  Biochemical function     catalytic activity     8 terms  


DOI no: 10.1016/j.jmb.2007.03.011 J Mol Biol 368:1172-1186 (2007)
PubMed id: 17391695  
A tick protein with a modified Kunitz fold inhibits human tryptase.
G.C.Paesen, C.Siebold, K.Harlos, M.F.Peacey, P.A.Nuttall, D.I.Stuart.
TdPI, a tick salivary gland product related to Kunitz/BPTI proteins is a potent inhibitor of human beta-tryptase. Kinetic assays suggest that three of the four catalytic sites of tryptase are blocked by TdPI, and that the inhibition of one of these involves a peptide flanking the Kunitz head. In the course of the inhibition, tryptase cleaves TdPI at several positions. Crystal structures of the TdPI head, on its own and in complex with trypsin, reveal features that are not found in classical Kunitz/BPTI proteins and suggest the mode of interaction with tryptase. The loop of TdPI connecting the beta-sheet with the C-terminal alpha-helix is shortened, the disulphide-bridge pattern altered and N and C termini separated to produce a highly pointed molecule capable of penetrating the cramped active sites of tryptase. TdPI accumulates in the cytosolic granules of mast cells, presumably suppressing inflammation in the host animal's skin by tryptase inhibition.
  Selected figure(s)  
Figure 5.
Figure 5. (a)–(c) Structures of the Kunitz-head domains of TdPI (a), BPTI (b) and ornithodorin (N-terminal head) (c). The ribbon presentations at the left are in rainbow colouring (N –terminus, cyan to C –terminus, red). The side-chains of the P1 residues of TdPI and BPTI are shown. The disulphide bridges (roman numerals) are in ball-and-stick presentation. The figures at the right show the solvent accessible surfaces of the heads (rotated 90° around the y axis, compared to the ribbon diagrams), coloured by electrostatic potential contoured at ±10 kT using GRASP (red, acidic; blue, basic). The arcs surround the N termini of the TdPI and BPTI structures. (d) Superimposed C^α traces of the heads of TdPI (red), BPTI (blue) and ornithodorin (green), in stereo, illustrating the shortening of loop L2 in both TdPI and ornithodorin, and the re-orientation and the widening of the base in TdPI.
Figure 6.
Figure 6. The structure of the TdPI-trypsin complex. (a) Superposition of the native (grey) and the complexed (red/blue) TdPI head. The red colour indicates areas where significant differences are found, while the blue colour indicates parts that are superimposable and contain a lower r.m.s.d. than 1.3 Å (calculated with SHP). Orientation is as in Figure 5(a). (b) Cartoon presentation of the complex of TdPI with trypsin (gold). Colour coding and orientation of TdPI are as in Figure 5(a). The P1-K39 is highlighted in sticks. (c) Superposition of TdPI (red), BPTI (blue) and LDTI (green) projected onto the TdPI-trypsin structure, in the same orientation as in Figure 5(b) (left), or 90° rotated around the y-axis (right). The orange arrows in the right panel indicate the more bulky region of BPTI in comparison to the tryptase inhibitors LDTI and TdPI. (d) Schematic representation of the interactions between TdPI and trypsin. Residues are depicted as sticks (N, blue; O, red; S, yellow; C(TdPI), orange; C(trypsin), black). H-bonds are shown in green, lengths are in Å. Red “eyelashes” show hydrophobic interactions.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 368, 1172-1186) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20231898 R.Bourgeas, M.J.Basse, X.Morelli, and P.Roche (2010).
Atomic analysis of protein-protein interfaces with known inhibitors: the 2P2I database.
  PLoS One, 5, e9598.  
19273185 I.M.Francischetti, A.Sa-Nunes, B.J.Mans, I.M.Santos, and J.M.Ribeiro (2009).
The role of saliva in tick feeding.
  Front Biosci, 14, 2051-2088.  
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