1bx7
From Proteopedia
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|PDB= 1bx7 |SIZE=350|CAPTION= <scene name='initialview01'>1bx7</scene>, resolution 1.20Å | |PDB= 1bx7 |SIZE=350|CAPTION= <scene name='initialview01'>1bx7</scene>, resolution 1.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bx7 OCA], [http://www.ebi.ac.uk/pdbsum/1bx7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bx7 RCSB]</span> | ||
}} | }} | ||
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[[Category: Sheldrick, G M.]] | [[Category: Sheldrick, G M.]] | ||
[[Category: Uson, I.]] | [[Category: Uson, I.]] | ||
| - | [[Category: SO4]] | ||
[[Category: anti-coagulant]] | [[Category: anti-coagulant]] | ||
[[Category: conformational flexibility]] | [[Category: conformational flexibility]] | ||
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[[Category: serine protease inhibitor]] | [[Category: serine protease inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:10:06 2008'' |
Revision as of 16:10, 30 March 2008
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| , resolution 1.20Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HIRUSTASIN FROM HIRUDO MEDICINALIS AT 1.2 ANGSTROMS
Overview
BACKGROUND: Leech-derived inhibitors have a prominent role in the development of new antithrombotic drugs, because some of them are able to block the blood coagulation cascade. Hirustasin, a serine protease inhibitor from the leech Hirudo medicinalis, binds specifically to tissue kallikrein and possesses structural similarity with antistasin, a potent factor Xa inhibitor from Haementeria officinalis. Although the 2.4 A structure of the hirustasin-kallikrein complex is known, classical methods such as molecular replacement were not successful in solving the structure of free hirustasin. RESULTS: Ab initio real/reciprocal space iteration has been used to solve the structure of free hirustasin using either 1.4 A room temperature data or 1.2 A low temperature diffraction data. The structure was also solved independently from a single pseudo-symmetric gold derivative using maximum likelihood methods. A comparison of the free and complexed structures reveals that binding to kallikrein causes a hinge-bending motion between the two hirustasin subdomains. This movement is accompanied by the isomerisation of a cis proline to the trans conformation and a movement of the P3, P4 and P5 residues so that they can interact with the cognate protease. CONCLUSIONS: The inhibitors from this protein family are fairly flexible despite being highly cross-linked by disulphide bridges. This intrinsic flexibility is necessary to adopt a conformation that is recognised by the protease and to achieve an optimal fit, such observations illustrate the pitfalls of designing inhibitors based on static lock-and-key models. This work illustrates the potential of new methods of structure solution that require less or even no prior phase information.
About this Structure
1BX7 is a Single protein structure of sequence from Hirudo medicinalis. Full crystallographic information is available from OCA.
Reference
The 1.2 A crystal structure of hirustasin reveals the intrinsic flexibility of a family of highly disulphide-bridged inhibitors., Uson I, Sheldrick GM, de La Fortelle E, Bricogne G, Di Marco S, Priestle JP, Grutter MG, Mittl PR, Structure. 1999 Jan 15;7(1):55-63. PMID:10368273
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