View source for 3apx


==Crystal structure of the A variant of human alpha1-acid glycoprotein and chlorpromazine complex==
<StructureSection load='3apx' size='340' side='right'caption='[[3apx]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3apx]] 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=3APX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3APX 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=Z80:3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</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=3apx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3apx OCA], [https://pdbe.org/3apx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3apx RCSB], [https://www.ebi.ac.uk/pdbsum/3apx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3apx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A1AG2_HUMAN A1AG2_HUMAN] Functions as transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability. Appears to function in modulating the activity of the immune system during the acute-phase reaction.<ref>PMID:21349832</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human alpha(1)-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type. In this study, we determined the crystal structures of this mutant hAGP alone and complexed with disopyramide (DSP), amitriptyline (AMT), and the nonspecific drug chlorpromazine (CPZ). The crystal structures revealed that the drug-binding pocket on the A variant is located within an eight-stranded beta-barrel, similar to that found in the F1*S variant and other lipocalin family proteins. However, the binding region of the A variant is narrower than that of the F1*S variant. In the crystal structures of complexes with DSP and AMT, the two aromatic rings of each drug interact with Phe-49 and Phe-112 at the bottom of the binding pocket. Although the structure of CPZ is similar to those of DSP and AMT, its fused aromatic ring system, which is extended in length by the addition of a chlorine atom, appears to dictate an alternative mode of binding, which explains its nonselective binding to the F1*S and A variant hAGPs. Modeling experiments based on the co-crystal structures suggest that, in complexes of DSP, AMT, or CPZ with the F1*S variant, Phe-114 sterically hinders interactions with DSP and AMT, but not CPZ.

Structural insights into differences in drug-binding selectivity between two forms of human alpha1-acid glycoprotein genetic variants, the A and F1*S forms.,Nishi K, Ono T, Nakamura T, Fukunaga N, Izumi M, Watanabe H, Suenaga A, Maruyama T, Yamagata Y, Curry S, Otagiri M J Biol Chem. 2011 Apr 22;286(16):14427-34. Epub 2011 Feb 24. PMID:21349832<ref>PMID:21349832</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3apx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Curry S]]
[[Category: Fukunaga N]]
[[Category: Izumi M]]
[[Category: Maruyama T]]
[[Category: Nakamura T]]
[[Category: Nishi K]]
[[Category: Ono T]]
[[Category: Otagiri M]]
[[Category: Suenaga A]]
[[Category: Watanabe H]]
[[Category: Yamagata Y]]