5e2p: Difference between revisions
New page: '''Unreleased structure''' The entry 5e2p is ON HOLD Authors: Wei, A. Description: FACTOR XIA IN COMPLEX WITH THE INHIBITOR (S)-N-(1-(5-CHLORO-2-(1H-TETRAZOL-1-YL)PHENETHYLAMINO)-1-OXO... |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==FACTOR XIA IN COMPLEX WITH THE INHIBITOR N-[(1S)-1-benzyl-2-[2-[5-chloro-2-(tetrazol-1-yl)phenyl]ethylamino]-2-oxo-ethyl]-4-hydroxy-2-oxo-1H-quinoline-6-carboxamide== | |||
<StructureSection load='5e2p' size='340' side='right'caption='[[5e2p]], [[Resolution|resolution]] 2.11Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5e2p]] is a 1 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=5E2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E2P 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]] 2.11Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7P0:N-[(1S)-1-BENZYL-2-[2-[5-CHLORO-2-(TETRAZOL-1-YL)PHENYL]ETHYLAMINO]-2-OXO-ETHYL]-4-HYDROXY-2-OXO-1H-QUINOLINE-6-CARBOXAMIDE'>7P0</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <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=5e2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e2p OCA], [https://pdbe.org/5e2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e2p RCSB], [https://www.ebi.ac.uk/pdbsum/5e2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e2p ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The synthesis, structural activity relationships (SAR), and selectivity profile of a potent series of phenylalanine diamide FXIa inhibitors will be discussed. Exploration of P1 prime and P2 prime groups led to the discovery of compounds with high FXIa affinity, good potency in our clotting assay (aPPT), and high selectivity against a panel of relevant serine proteases as exemplified by compound 21. Compound 21 demonstrated good in vivo efficacy (EC50=2.8muM) in the rabbit electrically induced carotid arterial thrombosis model (ECAT). | |||
Novel phenylalanine derived diamides as Factor XIa inhibitors.,Smith LM 2nd, Orwat MJ, Hu Z, Han W, Wang C, Rossi KA, Gilligan PJ, Pabbisetty KB, Osuna H, Corte JR, Rendina AR, Luettgen JM, Wong PC, Narayanan R, Harper TW, Bozarth JM, Crain EJ, Wei A, Ramamurthy V, Morin PE, Xin B, Zheng J, Seiffert DA, Quan ML, Lam PY, Wexler RR, Pinto DJ Bioorg Med Chem Lett. 2015 Nov 26. pii: S0960-894X(15)30296-1. doi:, 10.1016/j.bmcl.2015.11.089. PMID:26704266<ref>PMID:26704266</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Wei | <div class="pdbe-citations 5e2p" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Factor XIa 3D structures|Factor XIa 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Wei A]] | |||