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| | ==Solution structure of the Dbl-homology domain of Bcr-Abl== | | ==Solution structure of the Dbl-homology domain of Bcr-Abl== |
| - | <StructureSection load='5n6r' size='340' side='right'caption='[[5n6r]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5n6r' size='340' side='right'caption='[[5n6r]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5n6r]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N6R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5n6r]] 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=5N6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N6R FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCR, BCR1, D22S11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=5n6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n6r OCA], [https://pdbe.org/5n6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n6r RCSB], [https://www.ebi.ac.uk/pdbsum/5n6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n6r 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=5n6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n6r OCA], [http://pdbe.org/5n6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n6r RCSB], [http://www.ebi.ac.uk/pdbsum/5n6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n6r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/BCR_HUMAN BCR_HUMAN]] Note=A chromosomal aberration involving BCR is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). | + | [https://www.uniprot.org/uniprot/BCR_HUMAN BCR_HUMAN] Note=A chromosomal aberration involving BCR is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BCR_HUMAN BCR_HUMAN]] GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.<ref>PMID:1903516</ref> <ref>PMID:1657398</ref> | + | [https://www.uniprot.org/uniprot/BCR_HUMAN BCR_HUMAN] GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.<ref>PMID:1903516</ref> <ref>PMID:1657398</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | [[Category: Buchner L]] |
| - | [[Category: Buchner, L]] | + | [[Category: Dotsch V]] |
| - | [[Category: Dotsch, V]] | + | [[Category: Guntert P]] |
| - | [[Category: Guntert, P]] | + | [[Category: Hantschel O]] |
| - | [[Category: Hantschel, O]] | + | [[Category: Lohr F]] |
| - | [[Category: Lohr, F]] | + | [[Category: Reckel S]] |
| - | [[Category: Reckel, S]] | + | |
| - | [[Category: Bcr-abl]]
| + | |
| - | [[Category: Dbl-homology]]
| + | |
| - | [[Category: Helical bundle]]
| + | |
| - | [[Category: Leukemia]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
BCR_HUMAN Note=A chromosomal aberration involving BCR is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Function
BCR_HUMAN GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.[1] [2]
Publication Abstract from PubMed
The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH-PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.
Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase.,Reckel S, Gehin C, Tardivon D, Georgeon S, Kukenshoner T, Lohr F, Koide A, Buchner L, Panjkovich A, Reynaud A, Pinho S, Gerig B, Svergun D, Pojer F, Guntert P, Dotsch V, Koide S, Gavin AC, Hantschel O Nat Commun. 2017 Dec 13;8(1):2101. doi: 10.1038/s41467-017-02313-6. PMID:29235475[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Diekmann D, Brill S, Garrett MD, Totty N, Hsuan J, Monfries C, Hall C, Lim L, Hall A. Bcr encodes a GTPase-activating protein for p21rac. Nature. 1991 May 30;351(6325):400-2. PMID:1903516 doi:http://dx.doi.org/10.1038/351400a0
- ↑ Maru Y, Witte ON. The BCR gene encodes a novel serine/threonine kinase activity within a single exon. Cell. 1991 Nov 1;67(3):459-68. PMID:1657398
- ↑ Reckel S, Gehin C, Tardivon D, Georgeon S, Kukenshoner T, Lohr F, Koide A, Buchner L, Panjkovich A, Reynaud A, Pinho S, Gerig B, Svergun D, Pojer F, Guntert P, Dotsch V, Koide S, Gavin AC, Hantschel O. Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase. Nat Commun. 2017 Dec 13;8(1):2101. doi: 10.1038/s41467-017-02313-6. PMID:29235475 doi:http://dx.doi.org/10.1038/s41467-017-02313-6
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