View source for 6v89


==Human CtBP1 (28-375) in complex with AMP==
<StructureSection load='6v89' size='340' side='right'caption='[[6v89]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6v89]] is a 1 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=6V89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V89 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6v89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v89 OCA], [https://pdbe.org/6v89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v89 RCSB], [https://www.ebi.ac.uk/pdbsum/6v89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v89 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CTBP1_HUMAN CTBP1_HUMAN] Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation. Corepressor targeting diverse transcription regulators such as GLIS2. Has dehydrogenase activity.<ref>PMID:9858600</ref> <ref>PMID:15542832</ref> <ref>PMID:19103759</ref> <ref>PMID:12419229</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
C-terminal binding proteins (CtBPs) are cotranscriptional factors that play key roles in cell fate. We have previously shown that NAD(H) promotes the assembly of similar tetramers from either human CtBP1 and CtBP2 and that CtBP2 tetramer destabilizing mutants are defective for oncogenic activity. To assist structure-based design efforts for compounds that disrupt CtBP tetramerization, it is essential to understand how NAD(H) triggers tetramer assembly. Here, we investigate the moieties within NAD(H) that are responsible for triggering tetramer formation. Using multiangle light scattering (MALS), we show that ADP is able to promote tetramer formation of both CtBP1 and CtBP2, whereas AMP promotes tetramer assembly of CtBP1, but not CtBP2. Other NAD(H) moieties that lack the adenosine phosphate, including adenosine and those incorporating nicotinamide, all fail to promote tetramer assembly. Our crystal structures of CtBP1 with AMP reveal participation of the adenosine phosphate in the tetrameric interface, pinpointing its central role in NAD(H)-linked assembly. CtBP1 and CtBP2 have overlapping but unique roles, suggesting that a detailed understanding of their unique structural properties might have utility in the design of paralog-specific inhibitors. We investigated the different responses to AMP through a series of site-directed mutants at 13 positions. These mutations reveal a central role for a hinge segment, which we term the 120s hinge that connects the substrate with coenzyme-binding domains and influences nucleotide binding and tetramer assembly. Our results provide insight into suitable pockets to explore in structure-based drug design to interfere with cotranscriptional activity of CtBP in cancer.

NAD(H) phosphates mediate tetramer assembly of human C-terminal binding protein (CtBP).,Nichols JC, Schiffer CA, Royer WE Jr J Biol Chem. 2021 Jan-Jun;296:100351. doi: 10.1016/j.jbc.2021.100351. Epub 2021 , Jan 30. PMID:33524397<ref>PMID:33524397</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6v89" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Royer WE]]