1A5I

CATALYTIC DOMAIN OF VAMPIRE BAT (DESMODUS ROTUNDUS) SALIVA PLASMINOGEN ACTIVATOR IN COMPLEX WITH EGR-CMK (GLU-GLY-ARG CHLOROMETHYL KETONE)

Summary for 1A5I

• Entry DOI: 10.2210/pdb1a5i/pdb
• Related PRD ID: PRD_000288
• Descriptor: PLASMINOGEN ACTIVATOR, L-alpha-glutamyl-N-{(1S)-4-{[amino(iminio)methyl]amino}-1-[(1S)-2-chloro-1-hydroxyethyl]butyl}glycinamide (3 entities in total)
• Functional Keywords: serine protease, fibrinolytic enzymes, plasminogen activators, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Desmodus rotundus (common vampire bat)
• Cellular location: Secreted: P98119
• Total number of polymer chains: 1
• Total formula weight: 30112.46

Authors

Renatus, M.,Stubbs, M.T.,Bode, W. (deposition date: 1998-02-17, release date: 1999-03-23, Last modification date: 2024-10-30)

Primary citation

Renatus, M.,Stubbs, M.T.,Huber, R.,Bringmann, P.,Donner, P.,Schleuning, W.D.,Bode, W.
Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage.
Biochemistry, 36:13483-13493, 1997

PubMed 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.

PubMed: 9354616
DOI: 10.1021/bi971129x

Experimental method

X-RAY DIFFRACTION (2.9 Å)