5dv2
From Proteopedia
Crystal structure of human CNOT6L in complex with cytidine-5'-monophosphate
Structural highlights
FunctionCNO6L_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 PubMedHuman 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
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