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| | <StructureSection load='6g6k' size='340' side='right'caption='[[6g6k]], [[Resolution|resolution]] 1.35Å' scene=''> | | <StructureSection load='6g6k' size='340' side='right'caption='[[6g6k]], [[Resolution|resolution]] 1.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6g6k]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G6K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G6K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6g6k]] is a 4 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=6G6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6G6K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYC, BHLHE39 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MAX, BHLHD4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6g6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g6k OCA], [https://pdbe.org/6g6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6g6k RCSB], [https://www.ebi.ac.uk/pdbsum/6g6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6g6k ProSAT]</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=6g6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g6k OCA], [http://pdbe.org/6g6k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g6k RCSB], [http://www.ebi.ac.uk/pdbsum/6g6k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g6k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN]] Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors. Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:[http://omim.org/entry/113970 113970]]. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci. | + | [https://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN] Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors. Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:[https://omim.org/entry/113970 113970]. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN]] Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes. [[http://www.uniprot.org/uniprot/MAX_HUMAN MAX_HUMAN]] Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC-MAX complex is a transcriptional activator, whereas the MAD-MAX complex is a repressor. May repress transcription via the recruitment of a chromatin remodeling complex containing H3 'Lys-9' histone methyltransferase activity. | + | [https://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN] Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6g6k" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6g6k" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[C-Myc|C-Myc]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allen, M D]] | + | [[Category: Allen MD]] |
| - | [[Category: Zinzalla, G]] | + | [[Category: Zinzalla G]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Myc/max]]
| + | |
| Structural highlights
Disease
MYC_HUMAN Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors. Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:113970. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.
Function
MYC_HUMAN Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes.
Publication Abstract from PubMed
The c-MYC transcription factor is a master regulator of cell growth and proliferation and is an established target for cancer therapy. This basic helix-loop-helix Zip protein forms a heterodimer with its obligatory partner MAX, which binds to DNA via the basic region. Considerable research efforts are focused on targeting the heterodimerization interface and the interaction of the complex with DNA. The only available crystal structure is that of a c-MYC:MAX complex artificially tethered by an engineered disulfide linker and prebound to DNA. We have carried out a detailed structural analysis of the apo form of the c-MYC:MAX complex, with no artificial linker, both in solution using nuclear magnetic resonance (NMR) spectroscopy and by X-ray crystallography. We have obtained crystal structures in three different crystal forms, with resolutions between 1.35 and 2.2 A, that show extensive helical structure in the basic region. Determination of the alpha-helical propensity using NMR chemical shift analysis shows that the basic region of c-MYC and, to a lesser extent, that of MAX populate helical conformations. We have also assigned the NMR spectra of the c-MYC basic helix-loop-helix Zip motif in the absence of MAX and showed that the basic region has an intrinsic helical propensity even in the absence of its dimerization partner. The presence of helical structure in the basic regions in the absence of DNA suggests that the molecular recognition occurs via a conformational selection rather than an induced fit. Our work provides both insight into the mechanism of DNA binding and structural information to aid in the development of MYC inhibitors.
Crystal Structures and Nuclear Magnetic Resonance Studies of the Apo Form of the c-MYC:MAX bHLHZip Complex Reveal a Helical Basic Region in the Absence of DNA.,Sammak S, Hamdani N, Gorrec F, Allen MD, Freund SMV, Bycroft M, Zinzalla G Biochemistry. 2019 Jul 23;58(29):3144-3154. doi: 10.1021/acs.biochem.9b00296., Epub 2019 Jul 11. PMID:31260268[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sammak S, Hamdani N, Gorrec F, Allen MD, Freund SMV, Bycroft M, Zinzalla G. Crystal Structures and Nuclear Magnetic Resonance Studies of the Apo Form of the c-MYC:MAX bHLHZip Complex Reveal a Helical Basic Region in the Absence of DNA. Biochemistry. 2019 Jul 23;58(29):3144-3154. doi: 10.1021/acs.biochem.9b00296., Epub 2019 Jul 11. PMID:31260268 doi:http://dx.doi.org/10.1021/acs.biochem.9b00296
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