7jy3: Difference between revisions

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<table><tr><td colspan='2'>[[7jy3]] is a 4 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=7JY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JY3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7jy3]] is a 4 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=7JY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JY3 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]] 1.48&#8491;</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]] 1.48&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=O4B:1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE'>O4B</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=VUD:6-{(1S)-1-[(2-amino-6-fluoroquinolin-3-yl)oxy]ethyl}-5-(1H-pyrazol-1-yl)pyridin-2(1H)-one'>VUD</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=O4B:1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE'>O4B</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=VUD:6-[(1~{S})-1-(2-azanyl-6-fluoranyl-quinolin-3-yl)oxyethyl]-5-pyrazol-1-yl-1~{H}-pyridin-2-one'>VUD</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=7jy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jy3 OCA], [https://pdbe.org/7jy3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jy3 RCSB], [https://www.ebi.ac.uk/pdbsum/7jy3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jy3 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=7jy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jy3 OCA], [https://pdbe.org/7jy3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jy3 RCSB], [https://www.ebi.ac.uk/pdbsum/7jy3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jy3 ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues.
[https://www.uniprot.org/uniprot/HBA_HUMAN HBA_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues.
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== Publication Abstract from PubMed ==
Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (beta6 Glu --&gt; Val) on the beta-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clinical candidate PF-07059013 (23). The seminal hit molecule was discovered by virtual screening and confirmed through a series of biochemical and biophysical studies. After a significant optimization effort, we arrived at 23, a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-week multiple dose study using Townes SCD mice, 23 showed a 37.8% (+/-9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clinical trials.
PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease.,Gopalsamy A, Aulabaugh AE, Barakat A, Beaumont KC, Cabral S, Canterbury DP, Casimiro-Garcia A, Chang JS, Chen MZ, Choi C, Dow RL, Fadeyi OO, Feng X, France SP, Howard RM, Janz JM, Jasti J, Jasuja R, Jones LH, King-Ahmad A, Knee KM, Kohrt JT, Limberakis C, Liras S, Martinez CA, McClure KF, Narayanan A, Narula J, Novak JJ, O'Connell TN, Parikh MD, Piotrowski DW, Plotnikova O, Robinson RP, Sahasrabudhe PV, Sharma R, Thuma BA, Vasa D, Wei L, Wenzel AZ, Withka JM, Xiao J, Yayla HG J Med Chem. 2021 Jan 14;64(1):326-342. doi: 10.1021/acs.jmedchem.0c01518. Epub , 2020 Dec 24. PMID:33356244<ref>PMID:33356244</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7jy3" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Retrieved from "https://proteopedia.org/7jy3"