5dqf: Difference between revisions
New page: '''Unreleased structure''' The entry 5dqf is ON HOLD Authors: Handing, K.B., Shabalin, I.G., Majorek, K.A., Chruszcz, M., Almo, S.C., Minor, W., New York Structural Genomics Research Co... |
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==Horse Serum Albumin (ESA) in complex with Cetirizine== | |||
<StructureSection load='5dqf' size='340' side='right'caption='[[5dqf]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5dqf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DQF 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]] 2.15Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CZE:(2-{4-[(S)-(4-CHLOROPHENYL)(PHENYL)METHYL]PIPERAZIN-1-YL}ETHOXY)ACETIC+ACID'>CZE</scene>, <scene name='pdbligand=LCR:(2-{4-[(R)-(4-CHLOROPHENYL)(PHENYL)METHYL]PIPERAZIN-1-YL}ETHOXY)ACETIC+ACID'>LCR</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=5dqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dqf OCA], [https://pdbe.org/5dqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dqf RCSB], [https://www.ebi.ac.uk/pdbsum/5dqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dqf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ALBU_HORSE ALBU_HORSE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1A. Cetirizine is bound in two sites-a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews. | |||
Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.,Handing KB, Shabalin IG, Szlachta K, Majorek KA, Minor W Mol Immunol. 2016 Feb 17;71:143-151. doi: 10.1016/j.molimm.2016.02.003. PMID:26896718<ref>PMID:26896718</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5dqf" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Albumin 3D structures|Albumin 3D structures]] | ||
[[Category: Majorek | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Equus caballus]] | |||
[[Category: Large Structures]] | |||
[[Category: Almo SC]] | |||
[[Category: Chruszcz M]] | |||
[[Category: Handing KB]] | |||
[[Category: Majorek KA]] | |||
[[Category: Minor W]] | |||
[[Category: Shabalin IG]] | |||
Latest revision as of 11:49, 27 September 2023
Horse Serum Albumin (ESA) in complex with CetirizineHorse Serum Albumin (ESA) in complex with Cetirizine
Structural highlights
FunctionPublication Abstract from PubMedSerum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1A. Cetirizine is bound in two sites-a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews. Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.,Handing KB, Shabalin IG, Szlachta K, Majorek KA, Minor W Mol Immunol. 2016 Feb 17;71:143-151. doi: 10.1016/j.molimm.2016.02.003. PMID:26896718[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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