Proto-oncogene serine/threonine-protein kinase

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models Pim-1 complex with consensus peptide, inhibitor and Cl- ion 3cy2 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Disease 4 Structural highlights Function Proto-oncogene serine/threonine-protein kinase (Pim1) is the provirus integration site for Moloney murine leukemia virus 1[1]. Pim1 is involved in cell cycle progression, apoptosis, transcriptional activation and signaling pathways. Pim1 phosphorylates and inhibits proapoptotic proteins. For details see Student Project 6 for UMass Chemistry 423 Spring 2015. Relevance Pim1 is a progression marker in diffuse large B-cell lymphoma[2]. Disease Pim-1 plays a pivotal role in several tumor relevant signaling pathways and is relevant to colon carcinoma[3]. Structural highlights Pim1 is phosphorylated on serine 261 (PSer). The [4]. Water molecules are shown as red spheres.

3D Structures of pim-1

Updated on 04-December-2019 {{#tree:id=OrganizedByTopic|openlevels=0|

• Pim1; Domains catalytic 14-313; kinase 92-404

• • 1xqz, 1ywv, 4jx3 – hPim1 catalytic domain 14-313 – human
    
  • 1yxs – hPim1 catalytic domain (mutant)
    
  • 4jx3 – hPim1 kinase domain residues 92-404
    
  • 1xr1, 1yxt – hPim1 catalytic domain + AMPPNP
    
  • 1yxu – hPim1 catalytic domain + AMP
    
  • 1yxv – hPim1 catalytic domain + quinoline derivative
    
  • 3uix – hPim1 kinase domain residues 120-404 + quinoline derivative
    
  • 1yxx – hPim1 catalytic domain + indole derivative
    
  • 3a99 – hPim1 kinase domain + phosphoaminophosphonic acid adenylate
    
  • 2bzj, 2bzh, 2bzi – hPim1 catalytic domain (mutant) + organometallic ligand
    
  • 2oi4, 3bwf – hPim1 kinase domain (mutant) + organometallic ligand
    
  • 1xws, 4dtk, 4as0, 4alu, 4alv, 4alw, 4bzn, 4bzo, 6bsk, 5v80, 5toe, 5tex, 5tel, 5o11, 5o12, 5o13 – hPim1 kinase domain + inhibitor
    
  • 6ayd – hPim1 kinase domain (mutant)+ inhibitor
    
  • 2o3p, 2o63, 2o64, 2o65, 3jxw, 3jy0, 3jya, 3r00, 3r01, 3r02, 3r04, 3vbq, 3vbt, 3vbv, [[3vbw], 3vbx, 3vby, 3vc4, 3umx, 4enx, 4eny, 3umw, 4ll5, 4lm5, 3c4e, 5vuc, 5vub, 5vua, 4n70, 4n6z, 4n6y, 4mta, 4med, 4mbl, 4mbi, 4lmu, 4k1b, 4k18, 4k0y, 4iaa, 4i41, 6mt0 – hPim1 catalytic domain + inhibitor
    
  • 2j2i, 3we8 – hPim1 catalytic domain (mutant)+ inhibitor
    
  • 5tur - hPim1 + inhibitor
    

• Pim1 complex with consensus peptide

• • 2bil, 3cxw, 3cy2, 3cy3, 6qxk, 6pcw, 6pdi, 6pdn, 6pdo, 6pdp – hPim1 kinase domain + inhibitor + consensus peptide
    
  • 3jpv, 3qf9 - hPim1 catalytic domain + inhibitor + consensus peptide
    
  • 2c3i, 5ndt, 5n5m, 5n5l, 5n52, 5n51, 5n50, 5n4z, 5n4y, 5n4x, 5n4v, 5n4u, 5n4r, 5n4o, 5n4n, 5mzl – hPim1 kinase domain (mutant) + inhibitor + consensus peptide
    
  • 4gw8 – hPim1 catalytic domain (mutant) + inhibitor + consensus peptide
    
  • 2bzk – hPim1 kinase domain (mutant)+ AMPPNP + consensus peptide
    
  • 3ma3 – hPim1 catalytic domain + inhibitor + PSer + consensus peptide
    

• Pim1 containing phosphorylated Ser 261

• • 1yhs – hPim1 kinase domain + PSer + staurosporine
    
  • 1yi3, 2bik, 2xix, 2xiy, 2xiz, 2xj0, 2xj1, 2xj2, 4a7c – hPim1 kinase domain + PSer + inhibitor
    
  • 2obj, 3bgp, 3bgq, 3bgz, 3dcv, 3f2a, 3t9i - hPim1 catalytic domain + PSer + inhibitor
    
  • 1yi4 – hPim1 kinase domain + PSer + adenosine
    

• Pim1 raf see Serine/threonine protein kinase

}}

References

1. ↑ Bachmann M, Moroy T. The serine/threonine kinase Pim-1. Int J Biochem Cell Biol. 2005 Apr;37(4):726-30. PMID:15694833 doi:http://dx.doi.org/10.1016/j.biocel.2004.11.005
2. ↑ Brault L, Menter T, Obermann EC, Knapp S, Thommen S, Schwaller J, Tzankov A. PIM kinases are progression markers and emerging therapeutic targets in diffuse large B-cell lymphoma. Br J Cancer. 2012 Jul 24;107(3):491-500. doi: 10.1038/bjc.2012.272. Epub 2012 Jun, 21. PMID:22722314 doi:http://dx.doi.org/10.1038/bjc.2012.272
3. ↑ Weirauch U, Beckmann N, Thomas M, Grunweller A, Huber K, Bracher F, Hartmann RK, Aigner A. Functional role and therapeutic potential of the pim-1 kinase in colon carcinoma. Neoplasia. 2013 Jul;15(7):783-94. PMID:23814490
4. ↑ Huber K, Brault L, Fedorov O, Gasser C, Filippakopoulos P, Bullock AN, Fabbro D, Trappe J, Schwaller J, Knapp S, Bracher F. 7,8-Dichloro-1-oxo-beta-carbolines as a Versatile Scaffold for the Development of Potent and Selective Kinase Inhibitors with Unusual Binding Modes. J Med Chem. 2012 Jan 12;55(1):403-13. Epub 2012 Jan 3. PMID:22136433 doi:10.1021/jm201286z