7TW9

Structure of nsp14 N7-MethylTransferase domain fused with TELSAM bound to Sinefungin

PDB DOI: https://doi.org/10.2210/pdb7TW9/pdb

Classification: VIRAL PROTEIN
Organism(s): Severe acute respiratory syndrome coronavirus 2
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2022-02-06 Released: 2022-09-07
Deposition Author(s): Kottur, J., Aggarwal, A.K.
Funding Organization(s): Not funded

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.41 Å
R-Value Free: 0.232
R-Value Work: 0.192
R-Value Observed: 0.194

Starting Models: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

High-resolution structures of the SARS-CoV-2 N7-methyltransferase inform therapeutic development.

Kottur, J., Rechkoblit, O., Quintana-Feliciano, R., Sciaky, D., Aggarwal, A.K.

(2022) Nat Struct Mol Biol 29: 850-853

PubMed: 36075969 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41594-022-00828-1
Primary Citation of Related Structures:
7TW7, 7TW8, 7TW9

PubMed Abstract:
Emergence of SARS-CoV-2 coronavirus has led to millions of deaths globally. We present three high-resolution crystal structures of the SARS-CoV-2 nsp14 N7-methyltransferase core bound to S-adenosylmethionine (1.62 Å), S-adenosylhomocysteine (1.55 Å) and sinefungin (1.41 Å). We identify features of the methyltransferase core that are crucial for the development of antivirals and show SAH as the best scaffold for the design of antivirals against SARS-CoV-2 and other pathogenic coronaviruses.

Organizational Affiliation

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].

Macromolecule Content

Total Structure Weight: 36.2 kDa
Atom Count: 2,569
Modelled Residue Count: 261
Deposited Residue Count: 309
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Transcription factor ETV6,Proofreading exoribonuclease nsp14 chimera	A	309	Severe acute respiratory syndrome coronavirus 2	Mutation(s): 3 Gene Names: ETV6, TEL, TEL1, rep, 1a-1b EC: 3.1.13
UniProt & NIH Common Fund Data Resources
Find proteins for P41212 (Homo sapiens) Explore P41212 Go to UniProtKB: P41212
PHAROS: P41212 GTEx: ENSG00000139083
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2) Explore P0DTD1 Go to UniProtKB: P0DTD1
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Groups	P0DTD1P41212
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SFG (Subject of Investigation/LOI) Query on SFG Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	SINEFUNGIN C₁₅ H₂₃ N₇ O₅ LMXOHSDXUQEUSF-YECHIGJVSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A] mmCIF format, chain D [auth A]	D [auth A]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
EOH Query on EOH Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	ETHANOL C₂ H₆ O LFQSCWFLJHTTHZ-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
MOH Query on MOH Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A]	F [auth A], G [auth A], H [auth A], I [auth A], J [auth A]	METHANOL C H₄ O OKKJLVBELUTLKV-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A]