View source for 3ey6

==Crystal structure of the FK506-binding domain of human FKBP38==
<StructureSection load='3ey6' size='340' side='right' caption='[[3ey6]], [[Resolution|resolution]] 1.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ey6]] is a 1 chain structure with sequence 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=3EY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EY6 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f2d|2f2d]], [[2awg|2awg]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FKBP38, FKBP8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ey6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ey6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ey6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ey6 PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/FKBP8_HUMAN FKBP8_HUMAN]] Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis.<ref>PMID:12510191</ref> <ref>PMID:16176796</ref> <ref>PMID:15757646</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/ey/3ey6_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Bcl-2 inhibitor FKBP38 is regulated by the Ca(2+)-sensor calmodulin (CaM). Here we show a hitherto unknown low-affinity cation-binding site in the FKBP domain of FKBP38, which may afford an additional level of regulation based on electrostatic interactions. Fluorescence titration experiments indicate that in particular the physiologically relevant Ca(2+) ion binds to this site. NMR-based chemical shift perturbation data locate this cation-interaction site within the beta5-alpha1 loop (Leu90-Ile96) of the FKBP domain, which contains the acidic Asp92 and Asp94 side-chains. Binding constants were subsequently determined for K(+), Mg(2+), Ca(2+), and La(3+), indicating that the net charge and the radius of the ion influences the binding interaction. X-ray diffraction data furthermore show that the conformation of the beta5-alpha1 loop is influenced by the presence of a positively charged guanidinium group belonging to a neighboring FKBP38 molecule in the crystal lattice. The position of the cation-binding site has been further elucidated based on pseudocontact shift data obtained by NMR via titration with Tb(3+). Elimination of the Ca(2+)-binding capacity by substitution of the respective aspartate residues in a D92N/D94N double-substituted variant reduces the Bcl-2 affinity of the FKBP38(35-153)/CaM complex to the same degree as the presence of Ca(2+) in the wild-type protein. Hence, this charge-sensitive site in the FKBP domain participates in the regulation of FKBP38 function by enabling electrostatic interactions with ligand proteins and/or salt ions such as Ca(2+). Copyright (c) 2010 John Wiley &amp; Sons, Ltd.

A charge-sensitive loop in the FKBP38 catalytic domain modulates Bcl-2 binding.,Maestre-Martinez M, Haupt K, Edlich F, Neumann P, Parthier C, Stubbs MT, Fischer G, Lucke C J Mol Recognit. 2011 Jan;24(1):23-34. PMID:20140889<ref>PMID:20140889</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>

==See Also==
*[[FK506 binding protein|FK506 binding protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Peptidylprolyl isomerase]]
[[Category: Edlich, F]]
[[Category: Fischer, G]]
[[Category: Luecke, C]]
[[Category: Maestre-Martinez, M]]
[[Category: Neumann, P]]
[[Category: Parthier, C]]
[[Category: Stubbs, M T]]
[[Category: Apoptosis]]
[[Category: Beta half-barrel]]
[[Category: Host-virus interaction]]
[[Category: Immunophilin]]
[[Category: Isomerase]]
[[Category: Membrane]]
[[Category: Mitochondrion]]
[[Category: Phosphoprotein]]
[[Category: Ppiase]]
[[Category: Rotamase]]
[[Category: Tpr repeat]]
[[Category: Transmembrane]]