8hfh

From Proteopedia

(Difference between revisions)

Current revision

CENP-E motor domain in complex with AMPPNP and Mg2+

Structural highlights

8hfh 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 1.8Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CENPE_HUMAN Essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores. Plays a key role in the movement of chromosomes toward the metaphase plate during mitosis. Is a slow plus end-directed motor whose activity is essential for metaphase chromosome alignment. Couples chromosome position to microtubule depolymerizing activity. The highly processive microtubule-dependent motor activity of CENPE serves to power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss. Required for the efficient recruitment of BUBR1, MAD1 and MAD2 to attached and newly unattached kinetochores. Stimulates mammalian BUBR1 kinase activity. Accumulates just before mitosis at the G2 phase of the cell cycle.^[1] ^[2]

Publication Abstract from PubMed

Centromere-associated protein E (CENP-E) is a kinesin motor protein essential for mitosis and a new target for anticancer agents with less side effects. To rationally design anticancer drug candidates based on structure, it is important to determine the three-dimensional structure of the CENP-E motor domain bound to its inhibitor. Here, we report the first crystal structure of the CENP-E motor domain in complex with a non-hydrolysable ATP analogue, adenylyl-imidodiphosphate (AMPPNP). Furthermore, the structure is compared with the ADP-bound form of the CENP-E motor domain as well as the AMPPNP-bound forms of other kinesins. This study indicates that helix alpha4 of CENP-E participates in the slow binding of CENP-E to microtubules. These results will contribute to the development of anticancer drugs targeting CENP-E.

Crystal structure of the motor domain of centromere-associated protein E in complex with a non-hydrolysable ATP analogue.,Shibuya A, Suzuki A, Ogo N, Sawada JI, Asai A, Yokoyama H FEBS Lett. 2023 Feb 23. doi: 10.1002/1873-3468.14602. PMID:36823439^[3]

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

References

↑ Thrower DA, Jordan MA, Schaar BT, Yen TJ, Wilson L. Mitotic HeLa cells contain a CENP-E-associated minus end-directed microtubule motor. EMBO J. 1995 Mar 1;14(5):918-26. PMID:7889940
↑ Liu D, Ding X, Du J, Cai X, Huang Y, Ward T, Shaw A, Yang Y, Hu R, Jin C, Yao X. Human NUF2 interacts with centromere-associated protein E and is essential for a stable spindle microtubule-kinetochore attachment. J Biol Chem. 2007 Jul 20;282(29):21415-24. Epub 2007 May 29. PMID:17535814 doi:http://dx.doi.org/10.1074/jbc.M609026200
↑ Shibuya A, Suzuki A, Ogo N, Sawada JI, Asai A, Yokoyama H. Crystal structure of the motor domain of centromere-associated protein E in complex with a non-hydrolysable ATP analogue. FEBS Lett. 2023 Apr;597(8):1138-1148. PMID:36823439 doi:10.1002/1873-3468.14602

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8hfh"

Categories: Homo sapiens | Large Structures | Shibuya A | Yokoyama H

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8hfh]] 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=8HFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HFH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=8hfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hfh OCA], [https://pdbe.org/8hfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hfh RCSB], [https://www.ebi.ac.uk/pdbsum/8hfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hfh ProSAT]</span></td></tr>
 </table>

8hfh

From Proteopedia

Current revision

CENP-E motor domain in complex with AMPPNP and Mg2+

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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