1INY

A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES

PDB DOI: https://doi.org/10.2210/pdb1INY/pdb

Classification: HYDROLASE
Organism(s): Influenza A virus
Mutation(s): No

Deposited: 1994-09-26 Released: 1995-02-07
Deposition Author(s): White, C.L., Janakiraman, M.N., Laver, W.G., Philippon, C., Vasella, A., Air, G.M., Luo, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.40 ?
R-Value Work: 0.187
R-Value Observed: 0.187

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 2.1 of the entry. See complete history.

Literature

A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.

White, C.L., Janakiraman, M.N., Laver, W.G., Philippon, C., Vasella, A., Air, G.M., Luo, M.

(1995) J Mol Biol 245: 623-634

PubMed: 7844831 Search on PubMed
Primary Citation of Related Structures:
1INV, 1INW, 1INX, 1INY

PubMed Abstract:
A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.

Organizational Affiliation

Center for Macromolecular Crystallography, University of Alabama at Birmingham 35294.

Macromolecule Content

Total Structure Weight: 45.8 kDa
Atom Count: 3,257
Modelled Residue Count: 388
Deposited Residue Count: 388
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
INFLUENZA A SUBTYPE N9 NEURAMINIDASE	A	388	Influenza A virus	Mutation(s): 0 EC: 3.2.1.18
UniProt
Find proteins for P03472 (Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)) Explore P03472 Go to UniProtKB: P03472
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P03472
Glycosylation
Glycosylation Sites: 3	Glycosylation Focus chain A
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	B	7		N-Glycosylation	Interactions Focus chain B Interactions & Density Focus chain B
Glycosylation Resources
GlyTouCan: G46836GH GlyCosmos: G46836GH GlyGen: G46836GH

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
EQP Query on EQP Download Ideal Coordinates CCD File SDF format, chain F [auth A] MOL2 format, chain F [auth A] mmCIF format, chain F [auth A]	F [auth A]	(1R)-4-acetamido-1,5-anhydro-2,4-dideoxy-1-phosphono-D-glycero-D-galacto-octitol C₁₀ H₂₀ N O₉ P QITAGYVZDNZULE-IHICSVBISA-N		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A]	C [auth A], D [auth A]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Interactions & Density Focus chain C [auth A] Focus chain D [auth A]
CA Query on CA 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]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.40 ?
R-Value Work: 0.187
R-Value Observed: 0.187
Space Group: I 4 3 2

Unit Cell:

Length ( ? )	Angle ( ? )
a = 184.86	α = 90
b = 184.86	β = 90
c = 184.86	γ = 90

Software Package:

Software Name	Purpose
X-PLOR	model building
X-PLOR	refinement
X-PLOR	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 1995-02-07

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 1995-02-07
Type: Initial release
Version 1.1: 2008-03-03
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Database references, Derived calculations, Other, Structure summary
Version 2.1: 2024-10-23
Changes: Data collection, Database references, Structure summary