This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3vqu

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 18:58, 27 July 2022

CRYSTAL STRUCTURE OF HUMAN MPS1 CATALYTIC DOMAIN IN COMPLEX WITH 4-[(4-amino-5-cyano-6-ethoxypyridin-2- yl)amino]benzamide

Structural highlights

3vqu is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	TTK, MPS1, MPS1L1 (HUMAN)
Activity:	Dual-specificity kinase, with EC number 2.7.12.1
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

Monopolar spindle 1 (Mps1) is an attractive cancer drug target due to the important role that it plays in centrosome duplication, the spindle assembly checkpoint, and the maintenance of chromosomal stability. A design based on JNK inhibitors with an aminopyridine scaffold and subsequent modifications identified diaminopyridine 9 with an IC50 of 37 nM. The X-ray structure of 9 revealed that the Cys604 carbonyl group of the hinge region flips to form a hydrogen bond with the aniline NH group in 9. Further optimization of 9 led to 12 with improved cellular activity, suitable pharmacokinetic profiles, and good in vivo efficacy in the mouse A549 xenograft model. Moreover, 12 displayed excellent selectivity over 95 kinases, indicating the contribution of its unusual flipped-peptide conformation to its selectivity.

Diaminopyridine-based potent and selective mps1 kinase inhibitors binding to an unusual flipped-Peptide conformation.,Kusakabe K, Ide N, Daigo Y, Itoh T, Higashino K, Okano Y, Tadano G, Tachibana Y, Sato Y, Inoue M, Wada T, Iguchi M, Kanazawa T, Ishioka Y, Dohi K, Tagashira S, Kido Y, Sakamoto S, Yasuo K, Maeda M, Yamamoto T, Higaki M, Endoh T, Ueda K, Shiota T, Murai H, Nakamura Y ACS Med Chem Lett. 2012 Jun 6;3(7):560-4. doi: 10.1021/ml3000879. eCollection, 2012 Jul 12. PMID:24900510^[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
↑ Kusakabe K, Ide N, Daigo Y, Itoh T, Higashino K, Okano Y, Tadano G, Tachibana Y, Sato Y, Inoue M, Wada T, Iguchi M, Kanazawa T, Ishioka Y, Dohi K, Tagashira S, Kido Y, Sakamoto S, Yasuo K, Maeda M, Yamamoto T, Higaki M, Endoh T, Ueda K, Shiota T, Murai H, Nakamura Y. Diaminopyridine-based potent and selective mps1 kinase inhibitors binding to an unusual flipped-Peptide conformation. ACS Med Chem Lett. 2012 Jun 6;3(7):560-4. doi: 10.1021/ml3000879. eCollection, 2012 Jul 12. PMID:24900510 doi:http://dx.doi.org/10.1021/ml3000879

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3vqu"

@@ Line 3: / Line 3: @@
 <StructureSection load='3vqu' size='340' side='right'caption='[[3vqu]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3vqu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VQU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VQU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3vqu]] 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=3VQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VQU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=O22:4-[(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)AMINO]BENZAMIDE'>O22</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=O22:4-[(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)AMINO]BENZAMIDE'>O22</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TTK, MPS1, MPS1L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TTK, MPS1, MPS1L1 ([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'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vqu OCA], [http://pdbe.org/3vqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vqu RCSB], [http://www.ebi.ac.uk/pdbsum/3vqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vqu 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=3vqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vqu OCA], [https://pdbe.org/3vqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vqu RCSB], [https://www.ebi.ac.uk/pdbsum/3vqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vqu ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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 ==

3vqu

From Proteopedia

Revision as of 18:58, 27 July 2022

CRYSTAL STRUCTURE OF HUMAN MPS1 CATALYTIC DOMAIN IN COMPLEX WITH 4-[(4-amino-5-cyano-6-ethoxypyridin-2- yl)amino]benzamide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox