7L6T

Crystal Structure of SARS-CoV-2 Nsp16/10 Heterodimer in Complex with (m7GpppA2m)pUpUpApApA (Cap-1), S-Adenosyl-L-homocysteine (SAH) and two Magnesium (Mg) ions.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.78 Å
  • R-Value Free: 0.162 
  • R-Value Work: 0.141 
  • R-Value Observed: 0.142 

Starting Model: experimental
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This is version 2.0 of the entry. See complete history


Literature

Mn 2+ coordinates Cap-0-RNA to align substrates for efficient 2'- O -methyl transfer by SARS-CoV-2 nsp16.

Minasov, G.Rosas-Lemus, M.Shuvalova, L.Inniss, N.L.Brunzelle, J.S.Daczkowski, C.M.Hoover, P.Mesecar, A.D.Satchell, K.J.F.

(2021) Sci Signal 14

  • DOI: https://doi.org/10.1126/scisignal.abh2071
  • Primary Citation of Related Structures:  
    7JYY, 7L6R, 7L6T

  • PubMed Abstract: 

    Capping of viral messenger RNAs is essential for efficient translation, for virus replication, and for preventing detection by the host cell innate response system. The SARS-CoV-2 genome encodes the 2'- O -methyltransferase nsp16, which, when bound to the coactivator nsp10, uses S -adenosylmethionine (SAM) as a donor to transfer a methyl group to the first ribonucleotide of the mRNA in the final step of viral mRNA capping. Here, we provide biochemical and structural evidence that this reaction requires divalent cations, preferably Mn 2+ , and a coronavirus-specific four-residue insert. We determined the x-ray structures of the SARS-CoV-2 2'- O -methyltransferase (the nsp16-nsp10 heterodimer) in complex with its reaction substrates, products, and divalent metal cations. These structural snapshots revealed that metal ions and the insert stabilize interactions between the capped RNA and nsp16, resulting in the precise alignment of the ribonucleotides in the active site. Comparison of available structures of 2'- O -methyltransferases with capped RNAs from different organisms revealed that the four-residue insert unique to coronavirus nsp16 alters the backbone conformation of the capped RNA in the binding groove, thereby promoting catalysis. This insert is highly conserved across coronaviruses, and its absence in mammalian methyltransferases makes this region a promising site for structure-guided drug design of selective coronavirus inhibitors.


  • Organizational Affiliation

    Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine,,Chicago, IL 60611, USA.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
2'-O-methyltransferase300Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: rep1a-1b
EC: 2.1.1
UniProt
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTD1 
Go to UniProtKB:  P0DTD1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTD1
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Non-structural protein 10141Severe acute respiratory syndrome coronavirus 2Mutation(s): 0 
Gene Names: rep1a-1b
UniProt
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTD1 
Go to UniProtKB:  P0DTD1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTD1
Sequence Annotations
Expand
  • Reference Sequence

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains LengthOrganismImage
RNA (5'-D(*(M7G))-R(P*(A2M)P*UP*UP*A)-3')7synthetic construct
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH (Subject of Investigation/LOI)
Query on SAH

Download Ideal Coordinates CCD File 
G [auth A]S-ADENOSYL-L-HOMOCYSTEINE
C14 H20 N6 O5 S
ZJUKTBDSGOFHSH-WFMPWKQPSA-N
GLC
Query on GLC

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A]
alpha-D-glucopyranose
C6 H12 O6
WQZGKKKJIJFFOK-DVKNGEFBSA-N
BDF
Query on BDF

Download Ideal Coordinates CCD File 
L [auth B]beta-D-fructopyranose
C6 H12 O6
LKDRXBCSQODPBY-ARQDHWQXSA-N
ZN (Subject of Investigation/LOI)
Query on ZN

Download Ideal Coordinates CCD File 
J [auth B],
K [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
FMT
Query on FMT

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F [auth A]FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
E [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
MG (Subject of Investigation/LOI)
Query on MG

Download Ideal Coordinates CCD File 
D [auth A],
M [auth C]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 169.351α = 90
b = 169.351β = 90
c = 52.629γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2021-01-06
    Type: Initial release
  • Version 1.1: 2021-12-15
    Changes: Database references
  • Version 1.2: 2023-10-18
    Changes: Data collection, Refinement description
  • Version 2.0: 2024-03-06
    Changes: Data collection, Non-polymer description, Structure summary