5qqp
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[5qqp]] 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=5QQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QQP FirstGlance]. <br> | <table><tr><td colspan='2'>[[5qqp]] 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=5QQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QQP 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]] 2.08Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.08Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NR7:methyl+[( | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NR7:methyl+~{N}-[(12~{E},15~{S})-15-[(4~{S})-4-(3-chlorophenyl)-2-oxidanylidene-piperidin-1-yl]-9-oxidanylidene-8,17,19-triazatricyclo[14.2.1.0^{2,7}]nonadeca-1(18),2,4,6,12,16(19)-hexaen-5-yl]carbamate'>NR7</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=5qqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qqp OCA], [https://pdbe.org/5qqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qqp RCSB], [https://www.ebi.ac.uk/pdbsum/5qqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qqp ProSAT]</span></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=5qqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qqp OCA], [https://pdbe.org/5qqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qqp RCSB], [https://www.ebi.ac.uk/pdbsum/5qqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qqp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == 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. | [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 == | ||
| + | This manuscript describes the discovery of a series of macrocyclic inhibitors of FXIa with oral bioavailability. Assisted by structure based drug design and ligand bound X-ray crystal structures, the group linking the P1 moiety to the macrocyclic core was modified with the goal of reducing H-bond donors to improve pharmacokinetic performance versus 9. This effort resulted in the discovery of several cyclic P1 linkers, exemplified by 10, that are constrained mimics of the bioactive conformation displayed by the acrylamide linker of 9. These cyclic P1 linkers demonstrated enhanced bioavailability and improved potency. | ||
| + | |||
| + | Structure based design of macrocyclic factor XIa inhibitors: Discovery of cyclic P1 linker moieties with improved oral bioavailability.,Clark CG, Rossi KA, Corte JR, Fang T, Smallheer JM, De Lucca I, Nirschl DS, Orwat MJ, Pinto DJP, Hu Z, Wang Y, Yang W, Jeon Y, Ewing WR, Myers JE Jr, Sheriff S, Lou Z, Bozarth JM, Wu Y, Rendina A, Harper T, Zheng J, Xin B, Xiang Q, Luettgen JM, Seiffert DA, Wexler RR, Lam PYS Bioorg Med Chem Lett. 2019 Oct 1;29(19):126604. doi: 10.1016/j.bmcl.2019.08.008. , Epub 2019 Aug 16. PMID:31445854<ref>PMID:31445854</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5qqp" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
FACTOR XIA IN COMPLEX WITH THE INHIBITOR methyl [(5E,8S)-8-[(4S)-4-(3-chlorophenyl)-2-oxopiperidin-1-yl]-2-oxo-1,3,4,7,8,10-hexahydro-2H-12,9-(azeno)-1,10-benzodiazacyclotetradecin-15-yl]carbamate
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