PDBsum entry 1avg

Complex (blood coagulation/inhibitor)

PDB id: 1avg

Contents

Protein chains

41 a.a. *

259 a.a. *

142 a.a. *

Waters ×171

* Residue conservation analysis

PDB id:

1avg

Name:

Complex (blood coagulation/inhibitor)

Title:

Thrombin inhibitor from triatoma pallidipennis

Structure:

Thrombin. Chain: l. Other_details: thE C-terminal segment of the l-chain of one thrombin molecule is inserted in the active site of a neighboring thrombin molecule. Thrombin. Chain: h. Other_details: thE C-terminal segment of the l-chain of one thrombin molecule is inserted in the active site of a neighboring thrombin

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Organ: blood. Tissue: blood. Secretion: blood. Other_details: bovine thrombin was purified from from fresh ox blood according to reported protocols. Triatoma pallidipennis.

Biol. unit:

Trimer (from PQS)

Resolution:

2.60Å R-factor: 0.184 R-free: 0.275

Authors:

P.Fuentes-Prior,R.Huber,W.Bode

Key ref:

P.Fuentes-Prior et al. (1997). Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug. Proc Natl Acad Sci U S A, 94, 11845-11850. PubMed id: 9342325 DOI: 10.1073/pnas.94.22.11845

Date:

16-Sep-97 Release date: 30-Dec-98

Protein chain

P00735  (THRB_BOVIN) -  Prothrombin from Bos taurus

Seq: 625 a.a.

Struc: 41 a.a.

Protein chain

P00735  (THRB_BOVIN) -  Prothrombin from Bos taurus

Seq: 625 a.a.

Struc: 259 a.a.

Protein chain

Q27049  (TRIA_MECPA) -  Triabin from Meccus pallidipennis

Seq: 160 a.a.

Struc: 142 a.a.*

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

Enzyme reactions

• Enzyme class: Chains L, H: E.C.3.4.21.5 - thrombin.
• Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.

DOI no: 10.1073/pnas.94.22.11845

Proc Natl Acad Sci U S A 94:11845-11850 (1997)

PubMed id: 9342325

Structure of the thrombin complex with triabin, a lipocalin-like exosite-binding inhibitor derived from a triatomine bug.

P.Fuentes-Prior, C.Noeske-Jungblut, P.Donner, W.D.Schleuning, R.Huber, W.Bode.

ABSTRACT

Triabin, a 142-residue protein from the saliva of the blood-sucking triatomine bug Triatoma pallidipennis, is a potent and selective thrombin inhibitor. Its stoichiometric complex with bovine alpha-thrombin was crystallized, and its crystal structure was solved by Patterson search methods and refined at 2.6-A resolution to an R value of 0.184. The analysis revealed that triabin is a compact one-domain molecule essentially consisting of an eight-stranded beta-barrel. The eight strands A to H are arranged in the order A-C-B-D-E-F-G-H, with the first four strands exhibiting a hitherto unobserved up-up-down-down topology. Except for the B-C inversion, the triabin fold exhibits the regular up-and-down topology of lipocalins. In contrast to the typical ligand-binding lipocalins, however, the triabin barrel encloses a hydrophobic core intersected by a unique salt-bridge cluster. Triabin interacts with thrombin exclusively via its fibrinogen-recognition exosite. Surprisingly, most of the interface interactions are hydrophobic. A prominent exception represents thrombin's Arg-77A side chain, which extends into a hydrophobic triabin pocket forming partially buried salt bridges with Glu-128 and Asp-135 of the inhibitor. The fully accessible active site of thrombin in this complex is in agreement with its retained hydrolytic activity toward small chromogenic substrates. Impairment of thrombin's fibrinogen converting activity or of its thrombomodulin-mediated protein C activation capacity upon triabin binding is explained by usage of overlapping interaction sites of fibrinogen, thrombomodulin, and triabin on thrombin. These data demonstrate that triabin inhibits thrombin via a novel and unique mechanism that might be of interest in the context of potential therapeutic applications.

Selected figure(s)

Figure 2.
Fig. 2. Stereoview of the triabin ribbon. The eight strands A to H forming the - barrel are shown as yellow arrows, the N- and the^ C-terminal surface helices are shown as green helical ribbons, and the connecting loops are shown as green ropes. A few aromatic^ side chains, as well as the polar residues involved in the internal salt-bridge cluster, are shown with all nonhydrogen atoms. The^ view is, similar as in Fig. 1, approximately along the barrel axis of triabin i.e., through the more narrow barrel opening (front) toward the wider opening of the calyx (back). The figure was made^ with SETOR (8).

Figure 4.
Fig. 4. Closed-up stereo-view of the interaction interface between bovine thrombin and triabin. The contacting segments of thrombin (blue) and triabin (yellow) are shown as -carbon traces, and^ only the more important side chains are given with all atoms. Water molecules are omitted for the sake of simplicity. Orientation is similar to that seen in Figs. 1 and 2. The figure was made^ with SETOR (8).

Figures were selected by an automated process.