2j7t: Difference between revisions

Revision as of 14:37, 13 December 2023

Crystal structure of human serine threonine kinase-10 bound to SU11274

Structural highlights

2j7t 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 2Å
Ligands:	274, ACT, CA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

STK10_HUMAN The disease may be caused by mutations affecting the gene represented in this entry.^[1]

Function

STK10_HUMAN Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Protein kinase autophosphorylation of activation segment residues is a common regulatory mechanism in phosphorylation-dependent signalling cascades. However, the molecular mechanisms that guarantee specific and efficient phosphorylation of these sites have not been elucidated. Here, we report on three novel and diverse protein kinase structures that reveal an exchanged activation segment conformation. This dimeric arrangement results in an active kinase conformation in trans, with activation segment phosphorylation sites in close proximity to the active site of the interacting protomer. Analytical ultracentrifugation and chemical cross-linking confirmed the presence of dimers in solution. Consensus substrate sequences for each kinase showed that the identified activation segment autophosphorylation sites are non-consensus substrate sites. Based on the presented structural and functional data, a model for specific activation segment phosphorylation at non-consensus substrate sites is proposed that is likely to be common to other kinases from diverse subfamilies.

Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites.,Pike AC, Rellos P, Niesen FH, Turnbull A, Oliver AW, Parker SA, Turk BE, Pearl LH, Knapp S EMBO J. 2008 Feb 20;27(4):704-14. Epub 2008 Jan 31. PMID:18239682^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bignell G, Smith R, Hunter C, Stephens P, Davies H, Greenman C, Teague J, Butler A, Edkins S, Stevens C, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Clements J, Cole J, Dicks E, Edwards K, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Shepherd R, Small A, Solomon H, Stephens Y, Tofts C, Varian J, Webb A, West S, Widaa S, Yates A, Gillis AJ, Stoop HJ, van Gurp RJ, Oosterhuis JW, Looijenga LH, Futreal PA, Wooster R, Stratton MR. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults. Genes Chromosomes Cancer. 2006 Jan;45(1):42-6. PMID:16175573 doi:https://dx.doi.org/10.1002/gcc.20265
↑ Tao L, Wadsworth S, Mercer J, Mueller C, Lynn K, Siekierka J, August A. Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the CD28 responsive element in T-cells. Biochem J. 2002 Apr 1;363(Pt 1):175-82. PMID:11903060
↑ Walter SA, Cutler RE Jr, Martinez R, Gishizky M, Hill RJ. Stk10, a new member of the polo-like kinase kinase family highly expressed in hematopoietic tissue. J Biol Chem. 2003 May 16;278(20):18221-8. Epub 2003 Mar 13. PMID:12639966 doi:https://dx.doi.org/10.1074/jbc.M212556200
↑ Belkina NV, Liu Y, Hao JJ, Karasuyama H, Shaw S. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4707-12. doi:, 10.1073/pnas.0805963106. Epub 2009 Mar 2. PMID:19255442 doi:https://dx.doi.org/10.1073/pnas.0805963106
↑ Pike AC, Rellos P, Niesen FH, Turnbull A, Oliver AW, Parker SA, Turk BE, Pearl LH, Knapp S. Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites. EMBO J. 2008 Feb 20;27(4):704-14. Epub 2008 Jan 31. PMID:18239682 doi:10.1038/emboj.2008.8

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Bignell G, Smith R, Hunter C, Stephens P, Davies H, Greenman C, Teague J, Butler A, Edkins S, Stevens C, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Clements J, Cole J, Dicks E, Edwards K, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Shepherd R, Small A, Solomon H, Stephens Y, Tofts C, Varian J, Webb A, West S, Widaa S, Yates A, Gillis AJ, Stoop HJ, van Gurp RJ, Oosterhuis JW, Looijenga LH, Futreal PA, Wooster R, Stratton MR. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults. Genes Chromosomes Cancer. 2006 Jan;45(1):42-6. PMID:16175573 doi:https://dx.doi.org/10.1002/gcc.20265

[2] Tao L, Wadsworth S, Mercer J, Mueller C, Lynn K, Siekierka J, August A. Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the CD28 responsive element in T-cells. Biochem J. 2002 Apr 1;363(Pt 1):175-82. PMID:11903060

[3] Walter SA, Cutler RE Jr, Martinez R, Gishizky M, Hill RJ. Stk10, a new member of the polo-like kinase kinase family highly expressed in hematopoietic tissue. J Biol Chem. 2003 May 16;278(20):18221-8. Epub 2003 Mar 13. PMID:12639966 doi:https://dx.doi.org/10.1074/jbc.M212556200

[4] Belkina NV, Liu Y, Hao JJ, Karasuyama H, Shaw S. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4707-12. doi:, 10.1073/pnas.0805963106. Epub 2009 Mar 2. PMID:19255442 doi:https://dx.doi.org/10.1073/pnas.0805963106

[5] Pike AC, Rellos P, Niesen FH, Turnbull A, Oliver AW, Parker SA, Turk BE, Pearl LH, Knapp S. Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites. EMBO J. 2008 Feb 20;27(4):704-14. Epub 2008 Jan 31. PMID:18239682 doi:10.1038/emboj.2008.8

[1]

[2]

[3]

[4]

[5]

@@ Line 3: / Line 3: @@
 <StructureSection load='2j7t' size='340' side='right'caption='[[2j7t]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2j7t]] 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=2J7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J7T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2j7t]] 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=2J7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J7T FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=274:(3Z)-N-(3-CHLOROPHENYL)-3-({3,5-DIMETHYL-4-[(4-METHYLPIPERAZIN-1-YL)CARBONYL]-1H-PYRROL-2-YL}METHYLENE)-N-METHYL-2-OXOINDOLINE-5-SULFONAMIDE'>274</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2&#8491;</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_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=274:(3Z)-N-(3-CHLOROPHENYL)-3-({3,5-DIMETHYL-4-[(4-METHYLPIPERAZIN-1-YL)CARBONYL]-1H-PYRROL-2-YL}METHYLENE)-N-METHYL-2-OXOINDOLINE-5-SULFONAMIDE'>274</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=2j7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j7t OCA], [https://pdbe.org/2j7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j7t RCSB], [https://www.ebi.ac.uk/pdbsum/2j7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j7t ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/STK10_HUMAN STK10_HUMAN] The disease may be caused by mutations affecting the gene represented in this entry.<ref>PMID:16175573</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/STK10_HUMAN STK10_HUMAN] Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.<ref>PMID:11903060</ref> <ref>PMID:12639966</ref> <ref>PMID:19255442</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Arrowsmith CH]]
-[[Category: Arrowsmith, C H]]
+[[Category: Das S]]
-[[Category: Das, S]]
+[[Category: Debreczeni J]]
-[[Category: Debreczeni, J]]
+[[Category: Edwards A]]
-[[Category: Delft, F von]]
+[[Category: Eswaran J]]
-[[Category: Edwards, A]]
+[[Category: Fedorov O]]
-[[Category: Eswaran, J]]
+[[Category: Gorrec F]]
-[[Category: Fedorov, O]]
+[[Category: Knapp S]]
-[[Category: Gorrec, F]]
+[[Category: Papagrigoriou E]]
-[[Category: Knapp, S]]
+[[Category: Pike ACW]]
-[[Category: Papagrigoriou, E]]
+[[Category: Rellos P]]
-[[Category: Pike, A C.W]]
+[[Category: Savitsky P]]
-[[Category: Rellos, P]]
+[[Category: Sobott F]]
-[[Category: Savitsky, P]]
+[[Category: Sundstrom M]]
-[[Category: Sobott, F]]
+[[Category: Turnbull AP]]
-[[Category: Sundstrom, M]]
+[[Category: Ugochukwa E]]
-[[Category: Turnbull, A P]]
+[[Category: Umeano CC]]
-[[Category: Ugochukwa, E]]
+[[Category: Watt S]]
-[[Category: Umeano, C C]]
+[[Category: Weigelt J]]
-[[Category: Watt, S]]
+[[Category: Von Delft F]]
-[[Category: Weigelt, J]]
-[[Category: Atp-binding]]
-[[Category: Cell cycle progression]]
-[[Category: Disease mutation]]
-[[Category: Kinase]]
-[[Category: Nucleotide- binding]]
-[[Category: Phosphorylation]]
-[[Category: Serine/threonine- protein kinase]]
-[[Category: Transferase]]

2j7t: Difference between revisions

Revision as of 14:37, 13 December 2023

Crystal structure of human serine threonine kinase-10 bound to SU11274

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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