2v95: Difference between revisions

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[[Image:2v95.gif|left|200px]]<br />
<applet load="2v95" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2v95, resolution 1.93&Aring;" />
'''STRUTURE OF CORTICOSTEROID-BINDING GLOBULIN IN COMPLEX WITH CORTISOL'''<br />


==Overview==
==Structure of Corticosteroid-Binding Globulin in complex with Cortisol==
Corticosteroid-binding globulin (CBG) is a serine proteinase inhibitor, (serpin) family member that transports glucocorticoids in blood and, regulates their access to target cells. The 1.9 A crystal structure of rat, CBG shows that its steroid-binding site resembles the thyroxin-binding, site in the related serpin, thyroxin-binding globulin (TBG), and, mutagenesis studies have confirmed the contributions of key residues that, constitute the steroid-binding pocket. Unlike thyroxin-bound TBG, the, cortisol-bound CBG displays an "active" serpin conformation with the, proteinase-sensitive, reactive centre loop (RCL) fully expelled from the, regulatory beta-sheet A. Moreover, the CBG structure allows us to predict, that complete insertion of the proteolytically cleaved RCL into the serpin, ... [[http://ispc.weizmann.ac.il/pmbin/getpm?17644521 (full description)]]
<StructureSection load='2v95' size='340' side='right'caption='[[2v95]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2v95]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2v6d 2v6d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V95 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]] 1.93&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HCY:(11ALPHA,14BETA)-11,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE'>HCY</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=2v95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v95 OCA], [https://pdbe.org/2v95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v95 RCSB], [https://www.ebi.ac.uk/pdbsum/2v95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v95 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CBG_RAT CBG_RAT] Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.<ref>PMID:17644521</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/v9/2v95_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=2v95 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Corticosteroid-binding globulin (CBG) is a serine proteinase inhibitor (serpin) family member that transports glucocorticoids in blood and regulates their access to target cells. The 1.9A crystal structure of rat CBG shows that its steroid-binding site resembles the thyroxin-binding site in the related serpin, thyroxin-binding globulin, and mutagenesis studies have confirmed the contributions of key residues that constitute the steroid-binding pocket. Unlike thyroxin-bound thyroxin-binding globulin, the cortisol-bound CBG displays an "active" serpin conformation with the proteinase-sensitive, reactive center loop (RCL) fully expelled from the regulatory beta-sheet A. Moreover, the CBG structure allows us to predict that complete insertion of the proteolytically cleaved RCL into the serpin fold occurs in concert with a displacement and unwinding of helix D that would disrupt the steroid-binding site. This allosteric coupling between RCL positioning and occupancy of the CBG steroid-binding site, which resembles the ligand (glycosamino-glycan)-dependent activation of the thrombin inhibitory serpins heparin cofactor II and anti-thrombin RCLs, ensures both optimal recognition of CBG by target proteinases and efficient release of steroid to sites of action.


==About this Structure==
Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release.,Klieber MA, Underhill C, Hammond GL, Muller YA J Biol Chem. 2007 Oct 5;282(40):29594-603. Epub 2007 Jul 19. PMID:17644521<ref>PMID:17644521</ref>
2V95 is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]] with PDN as [[http://en.wikipedia.org/wiki/ligand ligand]]. This structure superseeds the now removed PDB entry 2V6D. Structure known Active Site: AC1. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2V95 OCA]].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Corticosteroid-binding globulin: structural basis for steroid transport and proteinase-triggered release., Klieber MA, Underhill C, Hammond GL, Muller YA, J Biol Chem. 2007 Jul 19;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17644521 17644521]
</div>
<div class="pdbe-citations 2v95" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Corticosteroid-binding globulin|Corticosteroid-binding globulin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Klieber MA]]
[[Category: Klieber, M.A.]]
[[Category: Muller YA]]
[[Category: Muller, Y.A.]]
[[Category: PDN]]
[[Category: cbg]]
[[Category: corticosteroid-binding globulin transport protein]]
[[Category: glucocorticoids]]
[[Category: glycoprotein]]
[[Category: lipid-binding]]
[[Category: rcl]]
[[Category: secreted]]
[[Category: serpin]]
[[Category: steroid transporter]]
[[Category: steroid-binding]]
[[Category: transport]]
 
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