View source for 5jb9


==Crystal structure of factor IXa K98T variant in complex with PPACK==
<StructureSection load='5jb9' size='340' side='right'caption='[[5jb9]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jb9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JB9 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]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=5jb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jb9 OCA], [https://pdbe.org/5jb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jb9 RCSB], [https://www.ebi.ac.uk/pdbsum/5jb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jb9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[https://omim.org/entry/306900 306900]; also known as Christmas disease.<ref>PMID:8295821</ref> <ref>PMID:2592373</ref> <ref>PMID:2743975</ref> <ref>PMID:6603618</ref> <ref>PMID:3009023</ref> <ref>PMID:3790720</ref> <ref>PMID:3401602</ref> <ref>PMID:3243764</ref> <ref>PMID:2713493</ref> <ref>PMID:2714791</ref> <ref>PMID:2773937</ref> <ref>PMID:2775660</ref> <ref>PMID:2753873</ref> <ref>PMID:2738071</ref> <ref>PMID:2472424</ref> <ref>PMID:2339358</ref> <ref>PMID:2372509</ref> <ref>PMID:2162822</ref> <ref>PMID:1958666</ref> <ref>PMID:1902289</ref> <ref>PMID:1346975</ref> <ref>PMID:1615485</ref> <ref>PMID:8257988</ref> <ref>PMID:8076946</ref> <ref>PMID:8199596</ref> <ref>PMID:7981722</ref> <ref>PMID:8680410</ref> <ref>PMID:9222764</ref> <ref>PMID:9590153</ref> <ref>PMID:9452115</ref> <ref>PMID:9600455</ref> <ref>PMID:10698280</ref> <ref>PMID:10094553</ref> <ref>PMID:11122099</ref> <ref>PMID:12588353</ref> <ref>PMID:12604421</ref>   Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide.  Defects in F9 are the cause of thrombophilia due to factor IX defect (THPH8) [MIM:[https://omim.org/entry/300807 300807]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN] Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Coagulation Factor IX is positioned at the merging point of the intrinsic and extrinsic blood coagulation cascades. Activated Factor IX (FIXa) serves as the trigger for amplification of coagulation through formation of the so-called Xase complex, which is a ternary complex of FIXa, its substrate Factor X, and the cofactor Factor VIIIa on the surface of activated platelets. Within the Xase complex the substrate turnover by FIXa is enhanced 200,000-fold, however, the mechanistic and structural basis for this dramatic enhancement remains only partly understood. A multi-faceted approach using enzymatic, biophysical and crystallographic methods to evaluate a key set of activity enhanced FIXa variants has demonstrated a delicately balanced, bidirectional network. Essential molecular interactions across multiple regions of the FIXa molecule cooperate in the maturation of the active site. This maturation is specifically facilitated by long range communication through the Ile212-Ile213 motif unique to FIXa and a flexibility of the 170-loop that is further dependent on the conformation in the Cys168-Cys182 disulphide bond. Ultimately the network consists of compensatory brakes (V16 and I213) and accelerators (Tyr99 and Phe174) that together allow for a subtle fine tuning of enzymatic activity.

Releasing the brakes in coagulation Factor IXa by cooperative maturation of the substrate binding site.,Kristensen LH, Olsen OH, Blouse GE, Brandstetter H Biochem J. 2016 May 19. pii: BCJ20160336. PMID:27208168<ref>PMID:27208168</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jb9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Factor IX 3D structures|Factor IX 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brandstetter H]]
[[Category: Kristensen LH]]