5dv4: Difference between revisions

Revision as of 07:12, 19 February 2020

Crystal structure of human CNOT6L in complex with neomycin

Structural highlights

5dv4 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:	NMY, SO4
Related:	5dv2
Gene:	CNOT6L, CCR4B (HUMAN)
Activity:	Poly(A)-specific ribonuclease, with EC number 3.1.13.4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CNO6L_HUMAN] Plays a role in the deadenylation of mRNAs in the cytoplasm. Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. May be involved in the deadenylation-dependent degradation of mRNAs through the 3'-UTR AU-rich element-mediated mechanism. Involved in deadenylation-dependent degradation of CDKN1B mRNA.^[1]

Publication Abstract from PubMed

Human CNOT6L/CCR4, a member of the endonuclease-exonuclease-phosphatase (EEP) family enzymes, is one of the two deadenylase enzymes in the conserved CCR4-NOT complex. Here, we report inhibitor-bound crystal structures of the human CNOT6L nuclease domain in complex with the nucleotide CMP and the aminoglycoside neomycin. Deadenylase activity assays show that nucleotides are effective inhibitors of both CNOT6L and CNOT7, with AMP more effective than other nucleotides, and that neomycin is a weak deadenylase inhibitor. Structural analysis shows that all inhibitors occupy the substrate and magnesium-binding sites of CNOT6L, suggesting that inhibitors compete with both substrate and divalent magnesium ions for overlapping binding sites.

Structural basis for inhibition of the deadenylase activity of human CNOT6L.,Zhang Q, Yan D, Guo E, Ding B, Yang W, Liu R, Yamamoto T, Bartlam M FEBS Lett. 2016 Apr;590(8):1270-9. doi: 10.1002/1873-3468.12160. Epub 2016 Apr, 15. PMID:27013054^[2]

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

References

↑ Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T. Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth. Mol Cell Biol. 2007 Jul;27(13):4980-90. Epub 2007 Apr 23. PMID:17452450 doi:MCB.02304-06
↑ Zhang Q, Yan D, Guo E, Ding B, Yang W, Liu R, Yamamoto T, Bartlam M. Structural basis for inhibition of the deadenylase activity of human CNOT6L. FEBS Lett. 2016 Apr;590(8):1270-9. doi: 10.1002/1873-3468.12160. Epub 2016 Apr, 15. PMID:27013054 doi:https://dx.doi.org/10.1002/1873-3468.12160

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OCA

[1] Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T. Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth. Mol Cell Biol. 2007 Jul;27(13):4980-90. Epub 2007 Apr 23. PMID:17452450 doi:MCB.02304-06

[2] Zhang Q, Yan D, Guo E, Ding B, Yang W, Liu R, Yamamoto T, Bartlam M. Structural basis for inhibition of the deadenylase activity of human CNOT6L. FEBS Lett. 2016 Apr;590(8):1270-9. doi: 10.1002/1873-3468.12160. Epub 2016 Apr, 15. PMID:27013054 doi:https://dx.doi.org/10.1002/1873-3468.12160

[1]

[2]

@@ Line 1: / Line 1: @@
 ==Crystal structure of human CNOT6L in complex with neomycin==
-<StructureSection load='5dv4' size='340' side='right' caption='[[5dv4]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='5dv4' size='340' side='right'caption='[[5dv4]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5dv4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DV4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5dv4]] 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=5DV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DV4 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NMY:NEOMYCIN'>NMY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dv2|5dv2]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNOT6L, CCR4B ([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/Poly(A)-specific_ribonuclease Poly(A)-specific ribonuclease], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.13.4 3.1.13.4] </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=5dv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dv4 OCA], [http://pdbe.org/5dv4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dv4 RCSB], [http://www.ebi.ac.uk/pdbsum/5dv4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dv4 ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bartlam, M]]
 [[Category: Zhang, Q]]

5dv4: Difference between revisions

Revision as of 07:12, 19 February 2020

Crystal structure of human CNOT6L in complex with neomycin

Structural highlights

Function

Publication Abstract from PubMed

References

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