1m9u
From Proteopedia
(New page: 200px<br /><applet load="1m9u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m9u, resolution 2.30Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1m9u.jpg|left|200px]]<br /><applet load="1m9u" size=" | + | [[Image:1m9u.jpg|left|200px]]<br /><applet load="1m9u" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1m9u, resolution 2.30Å" /> | caption="1m9u, resolution 2.30Å" /> | ||
'''Crystal Structure of Earthworm Fibrinolytic Enzyme Component A from Eisenia fetida'''<br /> | '''Crystal Structure of Earthworm Fibrinolytic Enzyme Component A from Eisenia fetida'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Earthworm fibrinolytic enzyme component A (EFEa) from Eisenia fetida is a | + | 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== | ==About this Structure== | ||
| - | 1M9U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Eisenia_fetida Eisenia fetida]. This structure | + | 1M9U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Eisenia_fetida Eisenia fetida]. This structure supersedes the now removed PDB entry 1IJ7. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M9U OCA]. |
==Reference== | ==Reference== | ||
| Line 20: | Line 20: | ||
[[Category: serine protease (elastase-like)]] | [[Category: serine protease (elastase-like)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:53:04 2008'' |
Revision as of 11:53, 21 February 2008
|
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 supersedes 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
Page seeded by OCA on Thu Feb 21 13:53:04 2008
