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==High resolution structure of Alpha-1-acid glycoprotein bound to potent anti-tumour compound UCN-01==
<StructureSection load='7oub' size='340' side='right'caption='[[7oub]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OUB 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]] 1.82&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UCN:7-HYDROXYSTAUROSPORINE'>UCN</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=7oub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oub OCA], [https://pdbe.org/7oub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oub RCSB], [https://www.ebi.ac.uk/pdbsum/7oub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oub ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The alpha1-acid glycoprotein (AGP) is an abundant blood plasma protein with important immunomodulatory functions coupled to endogenous and exogenous ligand binding properties. Its affinity for many drug-like structures, however, means AGP can have a significant effect on the pharmokinetics and pharmacodynamics of numerous small molecule therapeutics. Staurosporine, and its hydroxylated forms UCN-01 and UCN-02, are kinase inhibitors that have been investigated at length as anti-tumour compounds. Despite their potency, these compounds display poor pharmokinetics due to binding to both AGP variants, AGP1 and AGP2. Recent renewed interest in UCN-01 as a cytostatic protective agent prompted us to solve the structure of the AGP2/UCN-01 complex by X-ray crystallography, revealing for the first time the precise binding mode of UCN-01. Solution NMR suggests AGP2 undergoes a significant conformational change upon ligand binding, but also that it uses a common set of sidechains with which it captures key groups of UCN-01 and other small molecule ligands. We anticipate that this structure and supporting NMR data will facilitate rational re-design of small molecules that could evade AGP and therefore improve tissue distribution.

The structural basis for high affinity binding of alpha1-acid glycoprotein to the potent anti-tumour compound UCN-01.,Landin EJB, Williams C, Ryan SA, Bochel A, Akter N, Redfield C, Sessions RB, Dedi N, Taylor RJ, Crump MP J Biol Chem. 2021 Nov 7:101392. doi: 10.1016/j.jbc.2021.101392. PMID:34758357<ref>PMID:34758357</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Crump MP]]
[[Category: Landin EJB]]
[[Category: Williams C]]