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PDBsum entry 1a5i
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Hydrolase/hydrolase inhibitor PDB id
1a5i

 

 

 

 

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Contents
Protein chain
265 a.a. *
Ligands
0GJ
Waters ×33
* Residue conservation analysis
PDB id:
1a5i
Name: Hydrolase/hydrolase inhibitor
Title: Catalytic domain of vampire bat (desmodus rotundus) saliva plasminogen activator in complex with egr-cmk (glu-gly-arg chloromethyl ketone)
Structure: Plasminogen activator. Chain: a. Fragment: unp residues 213-477. Engineered: yes
Source: Desmodus rotundus. Common vampire bat. Organism_taxid: 9430. Organ: salivary glands. Expressed in: mesocricetus auratus. Expression_system_taxid: 10036. Expression_system_cell_line: bhk
Biol. unit: Dimer (from PQS)
Resolution:
2.90Å     R-factor:   0.198    
Authors: M.Renatus,M.T.Stubbs,W.Bode
Key ref:
M.Renatus et al. (1997). Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage. Biochemistry, 36, 13483-13493. PubMed id: 9354616 DOI: 10.1021/bi971129x
Date:
17-Feb-98     Release date:   23-Mar-99    
PROCHECK
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 Headers
 References

Protein chain
P98119  (URT1_DESRO) -  Salivary plasminogen activator alpha 1 from Desmodus rotundus
Seq:
Struc: 		477 a.a.
265 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.68  - t-plasminogen activator.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

 

 
DOI no: 10.1021/bi971129x Biochemistry 36:13483-13493 (1997)
PubMed id: 9354616  
 
 
Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage.
M.Renatus, M.T.Stubbs, R.Huber, P.Bringmann, P.Donner, W.D.Schleuning, W.Bode.
 
  ABSTRACT  
 
The saliva of the blood-eating vampire bat Desmodus rotundus contains plasminogen activators (PAs) that maintain the fluidity of the prey's blood by activating plasminogen and dissolving developing fibrin clots. D. rotundus salivary PAs (DSPAs) are composed of evolutionarily conserved domains reminiscent of human tissue-type PA (tPA), but their catalytic domain lacks a plasmin-sensitive "activation cleavage site". Despite this, all DSPAs are intrinsically active and enormously stimulated in the presence of fibrin. The recombinant catalytic domain of DSPAalpha1 has been crystallized in a covalent complex with Glu-Gly-Arg-chloromethyl ketone and its structure solved at 2.9 A resolution. The structure is similar to that of activated two-chain human tPA. Despite its single-chain status, the activation domain is observed in an enzymatically active conformation, with a functional substrate binding site and active site accommodating the peptidylmethylene inhibitor. The activation pocket, which normally receives the N-terminal Ile16, is occupied by the side chain of Lys156, whose distal ammonium group makes an internal salt bridge with the carboxylate group of Asp194. Lys156 is in a groove shielded from the bulk solvent by the intact "activation loop" (Gln10-Phe21), favoring Lys156-Asp194 salt bridge formation and stabilization of a functional substrate binding site. Together with the characteristic 186 insertion loop, the activation loop could act as a switch, effecting full single-chain enzymatic activity upon binding to fibrin.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18791694 A.Tellgren-Roth, K.Dittmar, S.E.Massey, C.Kemi, C.Tellgren-Roth, P.Savolainen, L.A.Lyons, and D.A.Liberles (2009).
Keeping the blood flowing-plasminogen activator genes and feeding behavior in vampire bats.
  Naturwissenschaften, 96, 39-47.  
18469556 B.Niego, A.Horvath, P.B.Coughlin, M.K.Pugsley, and R.L.Medcalf (2008).
Desmoteplase-mediated plasminogen activation and clot lysis are inhibited by the lysine analogue tranexamic acid.
  Blood Coagul Fibrinolysis, 19, 322-324.  
17311346 S.Sacquin-Mora, E.Laforet, and R.Lavery (2007).
Locating the active sites of enzymes using mechanical properties.
  Proteins, 67, 350-359.  
15561703 J.L.Arolas, J.Lorenzo, A.Rovira, J.Castellà, F.X.Aviles, and C.P.Sommerhoff (2005).
A carboxypeptidase inhibitor from the tick Rhipicephalus bursa: isolation, cDNA cloning, recombinant expression, and characterization.
  J Biol Chem, 280, 3441-3448.  
15939021 L.W.Yang, and I.Bahar (2005).
Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes.
  Structure, 13, 893-904.  
15892855 W.Bode (2005).
The structure of thrombin, a chameleon-like proteinase.
  J Thromb Haemost, 3, 2379-2388.  
15140132 G.Epple, W.D.Schleuning, G.Kettelgerdes, E.Kottgen, R.Gessner, and M.Praus (2004).
Prion protein stimulates tissue-type plasminogen activator-mediated plasmin generation via a lysine-binding site on kringle 2.
  J Thromb Haemost, 2, 962-968.  
12081498 S.Braud, B.F.Le Bonniec, C.Bon, and A.Wisner (2002).
The stratagem utilized by the plasminogen activator from the snake Trimeresurus stejnegeri to escape serpins.
  Biochemistry, 41, 8478-8484.  
10102985 H.Czapinska, and J.Otlewski (1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
  Eur J Biochem, 260, 571-595.  
  9524060 M.T.Stubbs, M.Renatus, and W.Bode (1998).
An active zymogen: unravelling the mystery of tissue-type plasminogen activator.
  Biol Chem, 379, 95.  
9733510 X.Wang, X.Lin, J.A.Loy, J.Tang, and X.C.Zhang (1998).
Crystal structure of the catalytic domain of human plasmin complexed with streptokinase.
  Science, 281, 1662-1665.
PDB code: 1bml
9434908 W.Bode, and M.Renatus (1997).
Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function.
  Curr Opin Struct Biol, 7, 865-872.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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