View source for 1bx8


==HIRUSTASIN FROM HIRUDO MEDICINALIS AT 1.4 ANGSTROMS==
<StructureSection load='1bx8' size='340' side='right'caption='[[1bx8]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1bx8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BX8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BX8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bx8 OCA], [https://pdbe.org/1bx8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bx8 RCSB], [https://www.ebi.ac.uk/pdbsum/1bx8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bx8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ANTA_HIRME ANTA_HIRME] Acts as an inhibitor of tissue kallikrein, trypsin, chymotrypsin and neutrophil cathepsin G.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:10368273</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1bx8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hirudo medicinalis]]
[[Category: Large Structures]]
[[Category: Bricogne G]]
[[Category: De La Fortelle E]]
[[Category: Di Marco S]]
[[Category: Gruetter MG]]
[[Category: Mittl PRE]]
[[Category: Priestle JP]]
[[Category: Sheldrick GM]]
[[Category: Uson I]]