5vcz: Difference between revisions

Revision as of 17:16, 11 December 2019

CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH Bosutinib isomer

Structural highlights

5vcz 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:	EDO, PEG, XZN
Related:	5vcv, 5vcw, 5vcx, 5vcy, 5vd0, 5vd1, 5vd3
Gene:	PKMYT1, MYT1 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PMYT1_HUMAN] Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development.^[1] ^[2]

Publication Abstract from PubMed

Members of the Wee family of kinases negatively regulate the cell cycle via phosphorylation of CDK1 and are considered potential drug targets. Herein, we investigated the structure-function relationship of human Wee1, Wee2 and Myt1 (PKMYT1). Purified recombinant full-length proteins and kinase domain constructs differed substantially in phosphorylation states and catalytic competency suggesting complex mechanisms of activation. A series of crystal structures revealed unique features that distinguish Wee1 and Wee2 from Myt1 and establish the structural basis of differential inhibition by the widely used Wee1 inhibitor MK-1775. Kinome profiling and cellular studies demonstrate that, in addition to Wee1 and Wee2, MK-1775 is an equally potent inhibitor of the polo-like kinase PLK1. Several previously unrecognized inhibitors of Wee kinases were discovered and characterized. Combined, the data provide a comprehensive view on the catalytic and structural properties of Wee kinases and a framework for the rational design of novel inhibitors thereof.

Structural basis of Wee kinases functionality and inactivation by diverse small molecule inhibitors.,Zhu JY, Cuellar RAD, Berndt N, Lee HE, Olesen SH, Martin MP, Jensen JT, Georg GI, Schonbrunn E J Med Chem. 2017 Aug 9. doi: 10.1021/acs.jmedchem.7b00996. PMID:28792760^[3]

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

References

↑ Liu F, Stanton JJ, Wu Z, Piwnica-Worms H. The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Mol Cell Biol. 1997 Feb;17(2):571-83. PMID:9001210
↑ Liu F, Rothblum-Oviatt C, Ryan CE, Piwnica-Worms H. Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes. Mol Cell Biol. 1999 Jul;19(7):5113-23. PMID:10373560
↑ Zhu JY, Cuellar RAD, Berndt N, Lee HE, Olesen SH, Martin MP, Jensen JT, Georg GI, Schonbrunn E. Structural basis of Wee kinases functionality and inactivation by diverse small molecule inhibitors. J Med Chem. 2017 Aug 9. doi: 10.1021/acs.jmedchem.7b00996. PMID:28792760 doi:https://dx.doi.org/10.1021/acs.jmedchem.7b00996

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Liu F, Stanton JJ, Wu Z, Piwnica-Worms H. The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Mol Cell Biol. 1997 Feb;17(2):571-83. PMID:9001210

[2] Liu F, Rothblum-Oviatt C, Ryan CE, Piwnica-Worms H. Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes. Mol Cell Biol. 1999 Jul;19(7):5113-23. PMID:10373560

[3] Zhu JY, Cuellar RAD, Berndt N, Lee HE, Olesen SH, Martin MP, Jensen JT, Georg GI, Schonbrunn E. Structural basis of Wee kinases functionality and inactivation by diverse small molecule inhibitors. J Med Chem. 2017 Aug 9. doi: 10.1021/acs.jmedchem.7b00996. PMID:28792760 doi:https://dx.doi.org/10.1021/acs.jmedchem.7b00996

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH Bosutinib isomer==
-<StructureSection load='5vcz' size='340' side='right' caption='[[5vcz]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+<StructureSection load='5vcz' size='340' side='right'caption='[[5vcz]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5vcz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VCZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VCZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5vcz]] 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=5VCZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VCZ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=XZN:4-[(3,5-DICHLORO-4-METHOXYPHENYL)AMINO]-6-METHOXY-7-[3-(4-METHYLPIPERAZIN-1-YL)PROPOXY]QUINOLINE-3-CARBONITRILE'>XZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vcv|5vcv]], [[5vcw|5vcw]], [[5vcx|5vcx]], [[5vcy|5vcy]], [[5vd0|5vd0]], [[5vd1|5vd1]], [[5vd3|5vd3]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKMYT1, MYT1 ([http://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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5vcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vcz OCA], [http://pdbe.org/5vcz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vcz RCSB], [http://www.ebi.ac.uk/pdbsum/5vcz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vcz ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Schonbrunn, E]]

5vcz: Difference between revisions

Revision as of 17:16, 11 December 2019

CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH Bosutinib isomer

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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