2bw7: Difference between revisions
No edit summary |
No edit summary |
||
| (20 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen== | ||
Catechol estrogens are steroid metabolites that elicit physiological | <StructureSection load='2bw7' size='340' side='right'caption='[[2bw7]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2bw7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Arthrospira_platensis Arthrospira platensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BW7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BW7 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ECS:2,3,17BETA-TRIHYDROXY-1,3,5(10)-ESTRATRIENE'>ECS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2bw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bw7 OCA], [https://pdbe.org/2bw7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bw7 RCSB], [https://www.ebi.ac.uk/pdbsum/2bw7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bw7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/O32393_ARTPT O32393_ARTPT] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bw/2bw7_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bw7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Catechol estrogens are steroid metabolites that elicit physiological responses through binding to a variety of cellular targets. We show here that catechol estrogens directly inhibit soluble adenylyl cyclases and the abundant trans-membrane adenylyl cyclases. Catechol estrogen inhibition is non-competitive with respect to the substrate ATP, and we solved the crystal structure of a catechol estrogen bound to a soluble adenylyl cyclase from Spirulina platensis in complex with a substrate analog. The catechol estrogen is bound to a newly identified, conserved hydrophobic patch near the active center but distinct from the ATP-binding cleft. Inhibitor binding leads to a chelating interaction between the catechol estrogen hydroxyl groups and the catalytic magnesium ion, distorting the active site and trapping the enzyme substrate complex in a non-productive conformation. This novel inhibition mechanism likely applies to other adenylyl cyclase inhibitors, and the identified ligand-binding site has important implications for the development of specific adenylyl cyclase inhibitors. | |||
A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen.,Steegborn C, Litvin TN, Hess KC, Capper AB, Taussig R, Buck J, Levin LR, Wu H J Biol Chem. 2005 Sep 9;280(36):31754-9. Epub 2005 Jul 7. PMID:16002394<ref>PMID:16002394</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 2bw7" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[3D Adenylyl cyclase 3D structures|3D Adenylyl cyclase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Arthrospira platensis]] | [[Category: Arthrospira platensis]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Buck | [[Category: Buck J]] | ||
[[Category: Capper | [[Category: Capper AB]] | ||
[[Category: Hess | [[Category: Hess KC]] | ||
[[Category: Levin | [[Category: Levin LR]] | ||
[[Category: Litvin | [[Category: Litvin TN]] | ||
[[Category: Steegborn | [[Category: Steegborn C]] | ||
[[Category: Taussig | [[Category: Taussig R]] | ||
[[Category: Wu | [[Category: Wu H]] | ||