View source for 5ncq


==Structure of the (SR) Ca2+-ATPase bound to a Tetrahydrocarbazole and TNP-ATP==
<StructureSection load='5ncq' size='340' side='right'caption='[[5ncq]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ncq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NCQ 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]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=128:SPIRO(2,4,6-TRINITROBENZENE[1,2A]-2O,3O-METHYLENE-ADENINE-TRIPHOSPHATE'>128</scene>, <scene name='pdbligand=8T8:(1~{S})-~{N}-[(4-bromophenyl)methyl]-7-(trifluoromethyloxy)-2,3,4,9-tetrahydro-1~{H}-carbazol-1-amine'>8T8</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PCW:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PCW</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=5ncq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ncq OCA], [https://pdbe.org/5ncq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ncq RCSB], [https://www.ebi.ac.uk/pdbsum/5ncq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ncq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AT2A1_RABIT AT2A1_RABIT] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have identified a series of tetrahydrocarbazoles as novel P-type ATPase inhibitors. Using a set of rationally designed analogues, we have analyzed their structure-activity relationship using functional assays, crystallographic data and computational modeling. We found that tetrahydrocarbazoles inhibit adenosine triphosphate (ATP) hydrolysis of the fungal H+-ATPase, depolarize the fungal plasma membrane and exhibit broad-spectrum antifungal activity. Comparative inhibition studies indicate that many tetrahydrocarbazoles also inhibit the mammalian Ca2+-ATPase (SERCA) and Na+,K+-ATPase with an even higher potency than Pma1. We have located the binding site for this compound class by crystallographic structure determination of a SERCA-tetrahydrocarbazole complex to 3.0 A resolution, finding that the compound binds to a region above the ion inlet channel of the ATPase. A homology model of the Candida albicans H+-ATPase based on this crystal structure, indicates that the compounds could bind to the same pocket and identifies pocket extensions that could be exploited for selectivity enhancement. The results of this study will aid further optimization towards selective H+-ATPase inhibitors as a new class of antifungal agents.

Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity.,Bublitz M, Kjellerup L, Cohrt KO, Gordon S, Mortensen AL, Clausen JD, Pallin TD, Hansen JB, Fuglsang AT, Dalby-Brown W, Winther AL PLoS One. 2018 Jan 2;13(1):e0188620. doi: 10.1371/journal.pone.0188620., eCollection 2018. PMID:29293507<ref>PMID:29293507</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ncq" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Brown WD]]
[[Category: Bublitz M]]
[[Category: Clausen JD]]
[[Category: Fuglsang A]]
[[Category: Gordon S]]
[[Category: Hansen JB]]
[[Category: Kjellerup L]]
[[Category: Mortensen AL]]
[[Category: O'Hanlon Cohrt K]]
[[Category: Pallin D]]
[[Category: Winther A-ML]]