4apc

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of Human NIMA-related Kinase 1 (NEK1)

Structural highlights

4apc is a 2 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 2.1Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NEK1_HUMAN Short rib-polydactyly syndrome, Majewski type. The disease is caused by mutations affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617).^[1]

Function

NEK1_HUMAN Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity. Implicated in the control of meiosis (By similarity). Involved in cilium assembly. In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death.^[2] ^[3]

Publication Abstract from PubMed

NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation. Here we report on the structure of the kinase domain of human NEK1 in its apo- and ATP-mimetic inhibitor bound forms. The inhibitor bound structure may allow the design of NEK specific chemo-sensitizing agents to act in conjunction with chemo- or radiation therapy of cancer cells. Furthermore, we characterized the dynamic protein interactome of NEK1 after DNA damage challenge with cisplatin. Our data suggest that NEK1 and its interaction partners trigger the DNA damage pathways responsible for correcting DNA crosslinks.

NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin.,Melo-Hanchuk TD, Slepicka PF, Meirelles GV, Basei FL, Lovato DV, Granato DC, Pauletti BA, Domingues RR, Leme AFP, Pelegrini AL, Lenz G, Knapp S, Elkins JM, Kobarg J Sci Rep. 2017 Jul 14;7(1):5445. doi: 10.1038/s41598-017-05325-w. PMID:28710492^[4]

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

References

↑ Thiel C, Kessler K, Giessl A, Dimmler A, Shalev SA, von der Haar S, Zenker M, Zahnleiter D, Stoss H, Beinder E, Abou Jamra R, Ekici AB, Schroder-Kress N, Aigner T, Kirchner T, Reis A, Brandstatter JH, Rauch A. NEK1 mutations cause short-rib polydactyly syndrome type majewski. Am J Hum Genet. 2011 Jan 7;88(1):106-14. doi: 10.1016/j.ajhg.2010.12.004. PMID:21211617 doi:http://dx.doi.org/10.1016/j.ajhg.2010.12.004
↑ Chen Y, Gaczynska M, Osmulski P, Polci R, Riley DJ. Phosphorylation by Nek1 regulates opening and closing of voltage dependent anion channel 1. Biochem Biophys Res Commun. 2010 Apr 9;394(3):798-803. doi:, 10.1016/j.bbrc.2010.03.077. Epub 2010 Mar 15. PMID:20230784 doi:http://dx.doi.org/10.1016/j.bbrc.2010.03.077
↑ Thiel C, Kessler K, Giessl A, Dimmler A, Shalev SA, von der Haar S, Zenker M, Zahnleiter D, Stoss H, Beinder E, Abou Jamra R, Ekici AB, Schroder-Kress N, Aigner T, Kirchner T, Reis A, Brandstatter JH, Rauch A. NEK1 mutations cause short-rib polydactyly syndrome type majewski. Am J Hum Genet. 2011 Jan 7;88(1):106-14. doi: 10.1016/j.ajhg.2010.12.004. PMID:21211617 doi:http://dx.doi.org/10.1016/j.ajhg.2010.12.004
↑ Melo-Hanchuk TD, Slepicka PF, Meirelles GV, Basei FL, Lovato DV, Granato DC, Pauletti BA, Domingues RR, Leme AFP, Pelegrini AL, Lenz G, Knapp S, Elkins JM, Kobarg J. NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin. Sci Rep. 2017 Jul 14;7(1):5445. doi: 10.1038/s41598-017-05325-w. PMID:28710492 doi:http://dx.doi.org/10.1038/s41598-017-05325-w

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4apc"

@@ Line 3: / Line 3: @@
 <StructureSection load='4apc' size='340' side='right'caption='[[4apc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4apc]] is a 2 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=4APC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4APC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4apc]] is a 2 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=4APC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4APC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.1&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4apc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4apc OCA], [http://pdbe.org/4apc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4apc RCSB], [http://www.ebi.ac.uk/pdbsum/4apc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4apc 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=4apc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4apc OCA], [https://pdbe.org/4apc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4apc RCSB], [https://www.ebi.ac.uk/pdbsum/4apc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4apc ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/NEK1_HUMAN NEK1_HUMAN]] Short rib-polydactyly syndrome, Majewski type. The disease is caused by mutations affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617).<ref>PMID:21211617</ref>
+[https://www.uniprot.org/uniprot/NEK1_HUMAN NEK1_HUMAN] Short rib-polydactyly syndrome, Majewski type. The disease is caused by mutations affecting the gene represented in this entry. In some cases NEK1 mutations result in disease phenotype in the presence of mutations in DYNC2H1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617).<ref>PMID:21211617</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/NEK1_HUMAN NEK1_HUMAN]] Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity. Implicated in the control of meiosis (By similarity). Involved in cilium assembly. In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death.<ref>PMID:20230784</ref> <ref>PMID:21211617</ref>
+[https://www.uniprot.org/uniprot/NEK1_HUMAN NEK1_HUMAN] Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity. Implicated in the control of meiosis (By similarity). Involved in cilium assembly. In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death.<ref>PMID:20230784</ref> <ref>PMID:21211617</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Arrowsmith C]]
-[[Category: Arrowsmith, C]]
+[[Category: Basei FL]]
-[[Category: Basei, F L]]
+[[Category: Bountra C]]
-[[Category: Bountra, C]]
+[[Category: Edwards A]]
-[[Category: Edwards, A]]
+[[Category: Elkins JM]]
-[[Category: Elkins, J M]]
+[[Category: Hanchuk TDM]]
-[[Category: Hanchuk, T D.M]]
+[[Category: Knapp S]]
-[[Category: Knapp, S]]
+[[Category: Kobarg J]]
-[[Category: Kobarg, J]]
+[[Category: Krojer T]]
-[[Category: Krojer, T]]
+[[Category: Lovato DV]]
-[[Category: Lovato, D V]]
+[[Category: Mahajan P]]
-[[Category: Mahajan, P]]
+[[Category: Meirelles GV]]
-[[Category: Meirelles, G V]]
+[[Category: Pike ACW]]
-[[Category: Pike, A C.W]]
+[[Category: Rellos P]]
-[[Category: Rellos, P]]
+[[Category: Szklarz M]]
-[[Category: Szklarz, M]]
+[[Category: Vollmar M]]
-[[Category: Vollmar, M]]
+[[Category: Zhang Y]]
-[[Category: Zhang, Y]]
-[[Category: Transferase]]

4apc

From Proteopedia

Current revision

Crystal Structure of Human NIMA-related Kinase 1 (NEK1)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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