PDBsum entry 3uir

Hydrolase/hydrolase inhibitor

PDB id: 3uir

Contents

Protein chains

243 a.a.

56 a.a.

Ligands

SO4 ×2

Waters ×104

PDB id:

3uir

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of the plasmin-textilinin-1 complex

Structure:

Plasmin light chain b. Chain: a, b. Synonym: microplasmin. Engineered: yes. Textilinin-1. Chain: c, d. Synonym: txln-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: plg. Expressed in: escherichia coli. Expression_system_taxid: 562. Pseudonaja textilis textilis. Eastern brown snake. Organism_taxid: 169397.

Resolution:

2.78Å R-factor: 0.211 R-free: 0.258

Authors:

L.W.Guddat,E.K.Millers,J.De Jersey,M.F.Lavin,P.M.Masci

Key ref:

E.K.Millers et al. (2013). The structure of human microplasmin in complex with textilinin-1, an aprotinin-like inhibitor from the Australian brown snake. Plos One, 8, e54104. PubMed id: 23335990

Date:

05-Nov-11 Release date: 26-Dec-12

Protein chains

P00747  (PLMN_HUMAN) -  Plasminogen from Homo sapiens

Seq: 810 a.a.

Struc: 243 a.a.

Protein chains

Q90WA1  (VKT1_PSETT) -  Kunitz-type serine protease inhibitor textilinin-1 from Pseudonaja textilis textilis

Seq: 83 a.a.

Struc: 56 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.4.21.7 - plasmin.
• Reaction: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products.

Plos One 8:e54104 (2013)

PubMed id: 23335990

The structure of human microplasmin in complex with textilinin-1, an aprotinin-like inhibitor from the Australian brown snake.

E.K.Millers, L.A.Johnson, G.W.Birrell, P.P.Masci, M.F.Lavin, J.de Jersey, L.W.Guddat.

ABSTRACT

Textilinin-1 is a Kunitz-type serine protease inhibitor from Australian brown snake venom. Its ability to potently and specifically inhibit human plasmin (K(i) = 0.44 nM) makes it a potential therapeutic drug as a systemic anti-bleeding agent. The crystal structures of the human microplasmin-textilinin-1 and the trypsin-textilinin-1 complexes have been determined to 2.78 Å and 1.64 Å resolution respectively, and show that textilinin-1 binds to trypsin in a canonical mode but to microplasmin in an atypical mode with the catalytic histidine of microplasmin rotated out of the active site. The space vacated by the histidine side-chain in this complex is partially occupied by a water molecule. In the structure of microplasminogen the χ(1) dihedral angle of the side-chain of the catalytic histidine is rotated by 67° from its "active" position in the catalytic triad, as exemplified by its location when microplasmin is bound to streptokinase. However, when textilinin-1 binds to microplasmin the χ(1) dihedral angle of this amino acid residue changes by -157° (i.e. in the opposite rotation direction compared to microplasminogen). The unusual mode of interaction between textilinin-1 and plasmin explains textilinin-1's selectivity for human plasmin over plasma kallikrein. This difference can be exploited in future drug design efforts.