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== | ==Solution structure of Minimal Mutant 1 (MM1): Multiple alanine mutant of non-native CHANCE domain== | ||
<StructureSection load='1wo3' size='340' side='right'caption='[[1wo3]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1wo3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WO3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1wo3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wo3 OCA], [https://pdbe.org/1wo3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wo3 RCSB], [https://www.ebi.ac.uk/pdbsum/1wo3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wo3 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[https://omim.org/entry/180849 180849]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Zinc binding motifs have received much attention in the area of protein design. Here, we have tested the suitability of a recently discovered nonnative zinc binding structure as a protein design scaffold. A series of multiple alanine mutants was created to investigate the minimal requirements for folding, and solution structures of these mutants showed that the original fold was maintained, despite changes in approximately 50% of the sequence. We next attempted to transplant binding faces from chosen bimolecular interactions onto one of these mutants, and many of the resulting "chimeras" were shown to adopt a native-like fold. These results both highlight the robust nature of small zinc binding domains and underscore the complexity of designing functional proteins, even using such small, highly ordered scaffolds as templates. | Zinc binding motifs have received much attention in the area of protein design. Here, we have tested the suitability of a recently discovered nonnative zinc binding structure as a protein design scaffold. A series of multiple alanine mutants was created to investigate the minimal requirements for folding, and solution structures of these mutants showed that the original fold was maintained, despite changes in approximately 50% of the sequence. We next attempted to transplant binding faces from chosen bimolecular interactions onto one of these mutants, and many of the resulting "chimeras" were shown to adopt a native-like fold. These results both highlight the robust nature of small zinc binding domains and underscore the complexity of designing functional proteins, even using such small, highly ordered scaffolds as templates. | ||
Assessment of the robustness of a serendipitous zinc binding fold: mutagenesis and protein grafting.,Sharpe BK, Liew CK, Kwan AH, Wilce JA, Crossley M, Matthews JM, Mackay JP Structure. 2005 Feb;13(2):257-66. PMID:15698569<ref>PMID:15698569</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1wo3" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]] | |||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Crossley | __TOC__ | ||
[[Category: Liew | </StructureSection> | ||
[[Category: Mackay | [[Category: Homo sapiens]] | ||
[[Category: Matthews | [[Category: Large Structures]] | ||
[[Category: Sharpe | [[Category: Crossley M]] | ||
[[Category: Wilce | [[Category: Liew CK]] | ||
[[Category: Mackay JP]] | |||
[[Category: Matthews JM]] | |||
[[Category: Sharpe BK]] | |||
[[Category: Wilce JA]] | |||