2x9e: Difference between revisions

Latest revision as of 10:37, 16 August 2023

HUMAN MPS1 IN COMPLEX WITH NMS-P715

Structural highlights

2x9e 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 3.1Å
Ligands:	SVE
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TTK_HUMAN Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.^[1]

Publication Abstract from PubMed

MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in a wide range of human tumors and is necessary for tumoral cell proliferation. Here we report the identification and characterization of NMS-P715, a selective and orally bioavailable MPS1 small-molecule inhibitor, which selectively reduces cancer cell proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates mitosis and affects kinetochore components localization causing massive aneuploidy and cell death in a variety of tumoral cell lines and inhibits tumor growth in preclinical cancer models. Inhibiting the SAC could represent a promising new approach to selectively target cancer cells. Cancer Res; 70(24); 10255-64. (c)2010 AACR.

Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase.,Colombo R, Caldarelli M, Mennecozzi M, Giorgini ML, Sola F, Cappella P, Perrera C, Depaolini SR, Rusconi L, Cucchi U, Avanzi N, Bertrand JA, Bossi RT, Pesenti E, Galvani A, Isacchi A, Colotta F, Donati D, Moll J Cancer Res. 2010 Dec 15;70(24):10255-64. PMID:21159646^[2]

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

References

↑ Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046. PMID:18243099 doi:10.1016/j.cell.2007.11.046
↑ Colombo R, Caldarelli M, Mennecozzi M, Giorgini ML, Sola F, Cappella P, Perrera C, Depaolini SR, Rusconi L, Cucchi U, Avanzi N, Bertrand JA, Bossi RT, Pesenti E, Galvani A, Isacchi A, Colotta F, Donati D, Moll J. Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase. Cancer Res. 2010 Dec 15;70(24):10255-64. PMID:21159646 doi:10.1158/0008-5472.CAN-10-2101

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046. PMID:18243099 doi:10.1016/j.cell.2007.11.046

[2] Colombo R, Caldarelli M, Mennecozzi M, Giorgini ML, Sola F, Cappella P, Perrera C, Depaolini SR, Rusconi L, Cucchi U, Avanzi N, Bertrand JA, Bossi RT, Pesenti E, Galvani A, Isacchi A, Colotta F, Donati D, Moll J. Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase. Cancer Res. 2010 Dec 15;70(24):10255-64. PMID:21159646 doi:10.1158/0008-5472.CAN-10-2101

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='2x9e' size='340' side='right'caption='[[2x9e]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2x9e]] 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=2X9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X9E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2x9e]] 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=2X9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X9E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SVE:N-(2,6-DIETHYLPHENYL)-1-METHYL-8-({4-[(1-METHYLPIPERIDIN-4-YL)CARBAMOYL]-2-(TRIFLUOROMETHOXY)PHENYL}AMINO)-4,5-DIHYDRO-1H-PYRAZOLO[4,3-H]QUINAZOLINE-3-CARBOXAMIDE'>SVE</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]] 3.1&#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;'>[[3hmo|3hmo]], [[3hmp|3hmp]], [[3h9f|3h9f]], [[3hmn|3hmn]], [[3gfw|3gfw]], [[2zmc|2zmc]], [[3cek|3cek]], [[2zmd|2zmd]], [[3dbq|3dbq]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SVE:N-(2,6-DIETHYLPHENYL)-1-METHYL-8-({4-[(1-METHYLPIPERIDIN-4-YL)CARBAMOYL]-2-(TRIFLUOROMETHOXY)PHENYL}AMINO)-4,5-DIHYDRO-1H-PYRAZOLO[4,3-H]QUINAZOLINE-3-CARBOXAMIDE'>SVE</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </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=2x9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x9e OCA], [https://pdbe.org/2x9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x9e RCSB], [https://www.ebi.ac.uk/pdbsum/2x9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x9e ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/TTK_HUMAN TTK_HUMAN]] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.<ref>PMID:18243099</ref>
+[https://www.uniprot.org/uniprot/TTK_HUMAN TTK_HUMAN] Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint.<ref>PMID:18243099</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Dual-specificity kinase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Avanzi, N]]
+[[Category: Avanzi N]]
-[[Category: Bertrand, J A]]
+[[Category: Bertrand JA]]
-[[Category: Bossi, R T]]
+[[Category: Bossi RT]]
-[[Category: Caldarelli, M]]
+[[Category: Caldarelli M]]
-[[Category: Cappella, P]]
+[[Category: Cappella P]]
-[[Category: Colombo, R]]
+[[Category: Colombo R]]
-[[Category: Colotta, F]]
+[[Category: Colotta F]]
-[[Category: Cucchi, U]]
+[[Category: Cucchi U]]
-[[Category: DePaolini, S R]]
+[[Category: DePaolini SR]]
-[[Category: Donati, D]]
+[[Category: Donati D]]
-[[Category: Galvani, A]]
+[[Category: Galvani A]]
-[[Category: Giorgini, M L]]
+[[Category: Giorgini ML]]
-[[Category: Isacchi, A]]
+[[Category: Isacchi A]]
-[[Category: Mennecozzi, M]]
+[[Category: Mennecozzi M]]
-[[Category: Moll, J]]
+[[Category: Moll J]]
-[[Category: Perrera, C]]
+[[Category: Perrera C]]
-[[Category: Pesenti, E]]
+[[Category: Pesenti E]]
-[[Category: Rusconi, L]]
+[[Category: Rusconi L]]
-[[Category: Sola, F]]
+[[Category: Sola F]]
-[[Category: Kinase]]
-[[Category: Mitotic checkpoint]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase]]
-[[Category: Tyrosine-protein kinase]]

2x9e: Difference between revisions

Latest revision as of 10:37, 16 August 2023

HUMAN MPS1 IN COMPLEX WITH NMS-P715

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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