7orc: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
New page: '''Unreleased structure''' The entry 7orc is ON HOLD Authors: Mota, C., Coelho, C., Santos Silva, T., Romao, M.J. Description: Human Aldehyde Oxidase in complex with Raloxifene [[Categ...
 
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
(4 intermediate revisions by the same user not shown)
Line 1: Line 1:
'''Unreleased structure'''


The entry 7orc is ON HOLD
==Human Aldehyde Oxidase in complex with Raloxifene==
<StructureSection load='7orc' size='340' side='right'caption='[[7orc]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ORC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ORC 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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=MTE:PHOSPHONIC+ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER'>MTE</scene>, <scene name='pdbligand=RAL:RALOXIFENE'>RAL</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=7orc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7orc OCA], [https://pdbe.org/7orc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7orc RCSB], [https://www.ebi.ac.uk/pdbsum/7orc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7orc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human aldehyde oxidase (hAOX1) is mainly present in the liver and has an emerging role in drug metabolism, since it accepts a wide range of molecules as substrates and inhibitors. Herein, we employed an integrative approach by combining NMR, X-ray crystallography, and enzyme inhibition kinetics to understand the inhibition modes of three hAOX1 inhibitors-thioridazine, benzamidine, and raloxifene. These integrative data indicate that thioridazine is a noncompetitive inhibitor, while benzamidine presents a mixed type of inhibition. Additionally, we describe the first crystal structure of hAOX1 in complex with raloxifene. Raloxifene binds tightly at the entrance of the substrate tunnel, stabilizing the flexible entrance gates and elucidating an unusual substrate-dependent mechanism of inhibition with potential impact on drug-drug interactions. This study can be considered as a proof-of-concept for an efficient experimental screening of prospective substrates and inhibitors of hAOX1 relevant in drug discovery.


Authors: Mota, C., Coelho, C., Santos Silva, T., Romao, M.J.
Interrogating the Inhibition Mechanisms of Human Aldehyde Oxidase by X-ray Crystallography and NMR Spectroscopy: The Raloxifene Case.,Mota C, Diniz A, Coelho C, Santos-Silva T, Esmaeeli M, Leimkuhler S, Cabrita EJ, Marcelo F, Romao MJ J Med Chem. 2021 Sep 9;64(17):13025-13037. doi: 10.1021/acs.jmedchem.1c01125., Epub 2021 Aug 20. PMID:34415167<ref>PMID:34415167</ref>


Description: Human Aldehyde Oxidase in complex with Raloxifene
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Santos Silva, T]]
<div class="pdbe-citations 7orc" style="background-color:#fffaf0;"></div>
[[Category: Coelho, C]]
== References ==
[[Category: Mota, C]]
<references/>
[[Category: Romao, M.J]]
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Coelho C]]
[[Category: Mota C]]
[[Category: Romao MJ]]
[[Category: Santos Silva T]]
Retrieved from "https://proteopedia.org/7orc"