9feh

Crystal structure of SARS-CoV-2 nsp14 methyltransferase domain in complex with the STM957 inhibitor

spinqualitylabelsall models 9feh, resolution 1.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9feh is a 1 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.99Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ETV6_HUMAN Note=A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML). Note=Chromosomal aberrations involving ETV6 are found in a form of acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1; translocation t(4;12)(q12;p13) with CHIC2. Note=Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1. Note=A chromosomal aberration involving ETV6 is found in a form of pre-B acute myeloid leukemia. Translocation t(9;12)(p24;p13) with JAK2. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6. Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2. Defects in ETV6 are a cause of myeloproliferative disorder chronic with eosinophilia (MPE) [MIM:131440. A hematologic disorder characterized by malignant eosinophils proliferation. Note=A chromosomal aberration involving ETV6 is found in many instances of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein. Defects in ETV6 are a cause of acute myelogenous leukemia (AML) [MIM:601626. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Note=A chromosomal aberration involving ETV6 is found in acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5. Function ETV6_HUMAN Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'.R1AB_SARS2 Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1-phosphate (ADRP).[UniProtKB:P0C6X7] Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]

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