3sxs: Difference between revisions

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<StructureSection load='3sxs' size='340' side='right'caption='[[3sxs]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
<StructureSection load='3sxs' size='340' side='right'caption='[[3sxs]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3sxs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SXS FirstGlance]. <br>
<table><tr><td colspan='2'>[[3sxs]] 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=3SXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SXS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PP2:1-TERT-BUTYL-3-(4-CHLORO-PHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLAMINE'>PP2</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.89&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3sxr|3sxr]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PP2:1-TERT-BUTYL-3-(4-CHLORO-PHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLAMINE'>PP2</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGMX1, ATK, BMX, BPK, BTK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=3sxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sxs OCA], [https://pdbe.org/3sxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sxs RCSB], [https://www.ebi.ac.uk/pdbsum/3sxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sxs ProSAT]</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=3sxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sxs OCA], [https://pdbe.org/3sxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sxs RCSB], [https://www.ebi.ac.uk/pdbsum/3sxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sxs ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/BMX_HUMAN BMX_HUMAN]] Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Plays also a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.<ref>PMID:9520419</ref> <ref>PMID:10688651</ref> <ref>PMID:11331870</ref> <ref>PMID:12370298</ref> <ref>PMID:12832404</ref> <ref>PMID:15788485</ref> <ref>PMID:18292575</ref> 
[https://www.uniprot.org/uniprot/BMX_HUMAN BMX_HUMAN] Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Plays also a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.<ref>PMID:9520419</ref> <ref>PMID:10688651</ref> <ref>PMID:11331870</ref> <ref>PMID:12370298</ref> <ref>PMID:12832404</ref> <ref>PMID:15788485</ref> <ref>PMID:18292575</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bone marrow kinase in the X chromosome (BMX), a member of the Tec family of tyrosine kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK) are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of BMX in complex with dasatinib at 2.4A resolution and PP2 at 1.9A resolution. The BMX structures reveal a typical kinase protein fold; with well ordered protein conformation that includes an open/extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to BMX in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The BMX structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective BMX inhibitors.
 
X-Ray Crystal Structure of Bone Marrow Kinase in the X Chromosome; a Tec Family Kinase.,Muckelbauer J, Sack JS, Ahmed N, Burke J, Chang CY, Gao M, Tino J, Xie D, Tebben AJ Chem Biol Drug Des. 2011 Aug 30. doi: 10.1111/j.1747-0285.2011.01230.x. PMID:21883956<ref>PMID:21883956</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3sxs" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Muckelbauer J]]
[[Category: Muckelbauer, J]]
[[Category: Sack J]]
[[Category: Sack, J]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 12:57, 1 March 2024

Crystal structure of BMX non-receptor tyrosine kinase complexed with PP2Crystal structure of BMX non-receptor tyrosine kinase complexed with PP2

Structural highlights

3sxs is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.89Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BMX_HUMAN Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Plays also a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.[1] [2] [3] [4] [5] [6] [7]

See Also

References

  1. ↑ Qiu Y, Robinson D, Pretlow TG, Kung HJ. Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3'-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3644-9. PMID:9520419
  2. ↑ Tsai YT, Su YH, Fang SS, Huang TN, Qiu Y, Jou YS, Shih HM, Kung HJ, Chen RH. Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation. Mol Cell Biol. 2000 Mar;20(6):2043-54. PMID:10688651
  3. ↑ Chen R, Kim O, Li M, Xiong X, Guan JL, Kung HJ, Chen H, Shimizu Y, Qiu Y. Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nat Cell Biol. 2001 May;3(5):439-44. PMID:11331870 doi:10.1038/35074500
  4. ↑ Pan S, An P, Zhang R, He X, Yin G, Min W. Etk/Bmx as a tumor necrosis factor receptor type 2-specific kinase: role in endothelial cell migration and angiogenesis. Mol Cell Biol. 2002 Nov;22(21):7512-23. PMID:12370298
  5. ↑ Abassi YA, Rehn M, Ekman N, Alitalo K, Vuori K. p130Cas Couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration. J Biol Chem. 2003 Sep 12;278(37):35636-43. Epub 2003 Jun 28. PMID:12832404 doi:http://dx.doi.org/10.1074/jbc.M306438200
  6. ↑ Chau CH, Clavijo CA, Deng HT, Zhang Q, Kim KJ, Qiu Y, Le AD, Ann DK. Etk/Bmx mediates expression of stress-induced adaptive genes VEGF, PAI-1, and iNOS via multiple signaling cascades in different cell systems. Am J Physiol Cell Physiol. 2005 Aug;289(2):C444-54. Epub 2005 Mar 23. PMID:15788485 doi:http://dx.doi.org/10.1152/ajpcell.00410.2004
  7. ↑ Semaan N, Alsaleh G, Gottenberg JE, Wachsmann D, Sibilia J. Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways. J Immunol. 2008 Mar 1;180(5):3485-91. PMID:18292575

3sxs, resolution 1.89Å

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