9DOJ

Influenza A virus polymerase PA subunit endonuclease domain bound to inhibitor Compound 19a

PDB DOI: https://doi.org/10.2210/pdb9DOJ/pdb

Classification: HYDROLASE/INHIBITOR
Organism(s): Influenza A virus
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2024-09-19 Released: 2025-01-29
Deposition Author(s): Hollenstein, K., Price, I.R., Eddins, M.J., Su, H.P.
Funding Organization(s): Not funded

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.48 ?
R-Value Free:
0.162 (Depositor), 0.169 (DCC)
R-Value Work:
0.123 (Depositor), 0.138 (DCC)
R-Value Observed:
0.125 (Depositor)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.0 of the entry. See complete history.

Literature

Highly Diastereoselective Access to Densely Functionalized Piperidine Cores of Influenza Endonuclease Inhibitors via a Metal-Free S N 1 Approach.

Zhang, Y., Sun, C., Guo, L., Zhao, K., Bennett, F., Lam, Y.H., Gao, Q., Ruhl, K.E., Pirnot, M.T., Emmert, M.H., Hollenstein, K., Eddins, M.J., Su, H.P., Shao, G., Song, C., Lo, M.M., Peng, F., Qi, J., Crowley, B.M., McCauley, J.A., Price, I.R.

(2025) J Org Chem 90: 1175-1179

PubMed: 39745425 Search on PubMed
DOI: https://doi.org/10.1021/acs.joc.4c02379
Primary Citation of Related Structures:
9DOJ

PubMed Abstract:
A novel, highly diastereoselective, and metal-free synthesis of multisubstituted piperidines via an S _N1 approach is reported in this study. The method allows for the preparation of highly functionalized compounds with exceptional diastereomeric selectivities and consistently reproducible yields. These compounds are of significant interest due to their remarkable biological activities toward influenza endonuclease.

Organizational Affiliation

Discovery Chemistry, MRL, Merck & Co. Inc., 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States.

Macromolecule Content

Total Structure Weight: 50.25 kDa
Atom Count: 3,900
Modelled Residue Count: 395
Deposited Residue Count: 418
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Polymerase acidic protein	A, B	209	Influenza A virus	Mutation(s): 0 Gene Names: PA EC: 3.1
UniProt
Find proteins for A0A646SQW7 (Influenza A virus) Explore A0A646SQW7 Go to UniProtKB: A0A646SQW7
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	A0A646SQW7
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
A1A8U (Subject of Investigation/LOI) Query on A1A8U Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain H [auth B] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B]	E [auth A], H [auth B]	(2aS,4aR,10bS,11S,12R)-4a-(2,2-difluoroethyl)-16-hydroxy-2-methyl-2,2a,3,4,4a,5,6,10b-octahydrobenzo[h]pyrido[1',2':1,6][1,2,4]triazino[2,3-a]quinoline-1,15-dione C₂₂ H₂₃ F₂ N₃ O₃ LMCZKNOBXDZFOL-UCNVEGJOSA-N		Interactions Focus chain E [auth A] Focus chain H [auth B] Interactions & Density Focus chain E [auth A] Focus chain H [auth B]
MLI Query on MLI Download Ideal Coordinates CCD File SDF format, chain I [auth B] MOL2 format, chain I [auth B] mmCIF format, chain I [auth B]	I [auth B]	MALONATE ION C₃ H₂ O₄ OFOBLEOULBTSOW-UHFFFAOYSA-L		Interactions Focus chain I [auth B] Interactions & Density Focus chain I [auth B]
MN Query on MN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain F [auth B] SDF format, chain G [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain F [auth B] MOL2 format, chain G [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain F [auth B] mmCIF format, chain G [auth B]	C [auth A], D [auth A], F [auth B], G [auth B]	MANGANESE (II) ION Mn WAEMQWOKJMHJLA-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain F [auth B] Focus chain G [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain F [auth B] Focus chain G [auth B]