1zuc: Difference between revisions

Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(8 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{Seed}}
[[Image:1zuc.png|left|200px]]


<!--
==Progesterone receptor ligand binding domain in complex with the nonsteroidal agonist tanaproget==
The line below this paragraph, containing "STRUCTURE_1zuc", creates the "Structure Box" on the page.
<StructureSection load='1zuc' size='340' side='right'caption='[[1zuc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1zuc]] is a 2 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=1ZUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZUC FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</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&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=T98:5-(4,4-DIMETHYL-2-THIOXO-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-6-YL)-1-METHYL-1H-PYRROLE-2-CARBONITRILE'>T98</scene></td></tr>
{{STRUCTURE_1zuc|  PDB=1zuc  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zuc OCA], [https://pdbe.org/1zuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zuc RCSB], [https://www.ebi.ac.uk/pdbsum/1zuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zuc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PRGR_HUMAN PRGR_HUMAN] The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</ref>  Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</ref>
== 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/zu/1zuc_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=1zuc ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Progesterone receptor (PR) agonists have several important applications in women's health, such as in oral contraception and post-menopausal hormone therapy. Currently, all PR agonists used clinically are steroids. Because of their interactions with other steroid receptors, steroid-metabolizing enzymes, or other steroid-signaling pathways, these drugs can pose significant side effects in some women. Efforts to discover novel nonsteroidal PR agonists with improved biological properties led to the discovery of tanaproget (TNPR). TNPR binds to the PR from various species with a higher relative affinity than reference steroidal progestins. In T47D cells, TNPR induces alkaline phosphatase activity with an EC(50) value of 0.1 nm, comparable with potent steroidal progestins such as medroxyprogesterone acetate (MPA) and trimegestone (TMG), albeit with a reduced efficacy ( approximately 60%). In a mammalian two-hybrid assay to measure PR agonist-induced interaction between steroid receptor co-activator-1 and PR, TNPR showed similar potency (EC(50) value of 0.02 nm) and efficacy to MPA and TMG. Importantly, in key animal models such as the rat ovulation inhibition assay, TNPR demonstrates full efficacy and an enhanced progestational potency (30-fold) when compared with MPA and TMG. Furthermore, TNPR has relatively weak interactions with other steroid receptors and binding proteins and little effect on cytochrome P450 metabolic pathways. Finally, the three-dimensional crystal structure of the PR ligand binding domain with TNPR has been delineated to demonstrate how this nonsteroidal ligand achieves its high binding affinity. Therefore, TNPR is a structurally novel and very selective PR agonist with an improved preclinical pharmacological profile.


===Progesterone receptor ligand binding domain in complex with the nonsteroidal agonist tanaproget===
Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget.,Zhang Z, Olland AM, Zhu Y, Cohen J, Berrodin T, Chippari S, Appavu C, Li S, Wilhem J, Chopra R, Fensome A, Zhang P, Wrobel J, Unwalla RJ, Lyttle CR, Winneker RC J Biol Chem. 2005 Aug 5;280(31):28468-75. Epub 2005 Jun 3. PMID:15937332<ref>PMID:15937332</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1zuc" style="background-color:#fffaf0;"></div>


<!--
==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_15937332}}, adds the Publication Abstract to the page
*[[Progesterone receptor|Progesterone receptor]]
(as it appears on PubMed at http://www.pubmed.gov), where 15937332 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_15937332}}
__TOC__
 
</StructureSection>
==About this Structure==
1ZUC is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZUC OCA].
 
==Reference==
<ref group="xtra">PMID:15937332</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Appavu, C.]]
[[Category: Large Structures]]
[[Category: Berrodin, T.]]
[[Category: Appavu C]]
[[Category: Chippari, S.]]
[[Category: Berrodin T]]
[[Category: Chopra, R.]]
[[Category: Chippari S]]
[[Category: Cohen, J.]]
[[Category: Chopra R]]
[[Category: Fensome, A.]]
[[Category: Cohen J]]
[[Category: Li, S.]]
[[Category: Fensome A]]
[[Category: Lyttle, C R.]]
[[Category: Li S]]
[[Category: Olland, A M.]]
[[Category: Lyttle CR]]
[[Category: Unwalla, R J.]]
[[Category: Olland AM]]
[[Category: Wilhem, J.]]
[[Category: Unwalla RJ]]
[[Category: Winneker, R C.]]
[[Category: Wilhem J]]
[[Category: Wrobel, J.]]
[[Category: Winneker RC]]
[[Category: Zhang, P.]]
[[Category: Wrobel J]]
[[Category: Zhang, Z.]]
[[Category: Zhang P]]
[[Category: Zhu, Y.]]
[[Category: Zhang Z]]
[[Category: Hormone]]
[[Category: Zhu Y]]
[[Category: Nonsteroidal agonist]]
[[Category: Progesterone]]
[[Category: Progesterone receptor]]
[[Category: Tanaproget]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 08:50:08 2009''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/1zuc"