6PZE

Crystal structure of human NA-45 Fab in complex with neuraminidase Y169aH mutant from A/Shanghai/2/2013 (H7N9)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.156 
  • R-Value Observed: 0.158 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Structural Basis of Protection against H7N9 Influenza Virus by Human Anti-N9 Neuraminidase Antibodies.

Zhu, X.Turner, H.L.Lang, S.McBride, R.Bangaru, S.Gilchuk, I.M.Yu, W.Paulson, J.C.Crowe Jr., J.E.Ward, A.B.Wilson, I.A.

(2019) Cell Host Microbe 26: 729

  • DOI: https://doi.org/10.1016/j.chom.2019.10.002
  • Primary Citation of Related Structures:  
    6PZD, 6PZE, 6PZF, 6PZG, 6PZH, 6PZW, 6PZY, 6PZZ, 6U02

  • PubMed Abstract: 

    Influenza virus neuraminidase (NA) is a major target for small-molecule antiviral drugs. Antibodies targeting the NA surface antigen could also inhibit virus entry and egress to provide host protection. However, our understanding of the nature and range of target epitopes is limited because of a lack of human antibody structures with influenza neuraminidase. Here, we describe crystal and cryogenic electron microscopy (cryo-EM) structures of NAs from human-infecting avian H7N9 viruses in complex with five human anti-N9 antibodies, systematically defining several antigenic sites and antibody epitope footprints. These antibodies either fully or partially block the NA active site or bind to epitopes distant from the active site while still showing neuraminidase inhibition. The inhibition of antibodies to NAs was further analyzed by glycan array and solution-based NA activity assays. Together, these structural studies provide insights into protection by anti-NA antibodies and templates for the development of NA-based influenza virus vaccines and therapeutics.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neuraminidase393Influenza A virus (A/Shanghai/02/2013(H7N9))Mutation(s): 1 
EC: 3.2.1.18
UniProt
Find proteins for R4NFR6 (Influenza A virus)
Explore R4NFR6 
Go to UniProtKB:  R4NFR6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupR4NFR6
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
NA-45 FAB LIGHT CHAINB [auth L]217Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
NA-45 FAB HEAVY CHAINC [auth H]237Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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-glucopyranoseD [auth B]10N-Glycosylation
Glycosylation Resources
GlyTouCan:  G91704UR
GlyCosmos:  G91704UR
GlyGen:  G91704UR
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseE [auth C]2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CA (Subject of Investigation/LOI)
Query on CA

Download Ideal Coordinates CCD File 
F [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.197 
  • R-Value Work: 0.156 
  • R-Value Observed: 0.158 
  • Space Group: P 4 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 161.268α = 90
b = 161.268β = 90
c = 87.382γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesU19 AI117905
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesHHSN272201400024C

Revision History  (Full details and data files)

  • Version 1.0: 2019-12-04
    Type: Initial release
  • Version 1.1: 2019-12-25
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-11
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary