1m9u

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1m9u, resolution 2.30Å

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Crystal Structure of Earthworm Fibrinolytic Enzyme Component A from Eisenia fetida

Overview

Earthworm fibrinolytic enzyme component A (EFEa) from Eisenia fetida is a, strong fibrinolytic enzyme that not only directly degrades fibrin, but, also activates plasminogen. Proteolytic assays further revealed that it, cleaved behind various P1 residue types. The crystal structure of EFEa was, determined using the MIR method and refined to 2.3A resolution. The, enzyme, showing the overall polypeptide fold of chymotrypsin-like serine, proteases, possesses essential S1 specificity determinants characteristic, of elastase. However, the beta strand at the west rim of the S1, specificity pocket is significantly elongated by a unique four-residue, insertion (Ser-Ser-Gly-Leu) after Val217, which not only provides, additional substrate hydrogen binding sites for distal P residues, but, also causes extension of the S1 pocket at the south rim. The S2 subsite of, the enzyme was partially occluded by the bulky side-chain of residue, Tyr99. Structure-based inhibitor modeling demonstrated that EFEa's S1, specificity pocket was preferable for elastase-specific small hydrophobic, P1 residues, while its accommodation of long and/or bulky P1 residues was, also feasible if enhanced binding of the substrate and induced fit of the, S1 pocket were achieved. EFEa is thereby endowed with relatively broad, substrate specificity, including the dual fibrinolysis. The presence of, Tyr99 at the S2 subsite indicates a preference for P2-Gly, while an, induced fit of Tyr99 was also suggested for accommodation of bigger P2, residues. This structure is the first reported for an earthworm, fibrinolytic enzyme component and serine protease originating from annelid, worms.

About this Structure

1M9U is a Single protein structure of sequence from Eisenia fetida. This structure superseeds the now removed PDB entry 1IJ7. Full crystallographic information is available from OCA.

Reference

Crystal structure of earthworm fibrinolytic enzyme component a: revealing the structural determinants of its dual fibrinolytic activity., Tang Y, Liang D, Jiang T, Zhang J, Gui L, Chang W, J Mol Biol. 2002 Aug 2;321(1):57-68. PMID:12139933

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