4WZ9

APN1 from Anopheles gambiae

PDB DOI: https://doi.org/10.2210/pdb4WZ9/pdb

Classification: HYDROLASE
Organism(s): Anopheles gambiae, Drosophila
Expression System: Drosophila
Mutation(s): No

Deposited: 2014-11-19 Released: 2015-06-17
Deposition Author(s): Atkinson, S.C., Armistead, J.S., Mathias, D.K., Sandeu, M.M., Tao, D., Borhani-Dizaji, N., Morlais, I., Dinglasan, R.R., Borg, N.A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.65 Å
R-Value Free: 0.254
R-Value Work: 0.200
R-Value Observed: 0.203

wwPDB Validation 3D Report Full Report

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

Literature

The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope.

Atkinson, S.C., Armistead, J.S., Mathias, D.K., Sandeu, M.M., Tao, D., Borhani-Dizaji, N., Tarimo, B.B., Morlais, I., Dinglasan, R.R., Borg, N.A.

(2015) Nat Struct Mol Biol 22: 532-539

PubMed: 26075520 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/nsmb.3048
Primary Citation of Related Structures:
4WZ9

PubMed Abstract:
Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however, AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antibodies functionally block parasite transmission have remained elusive. Here we present the 2.65-Å crystal structure of AnAPN1 and the immunoreactivity and transmission-blocking profiles of three monoclonal antibodies (mAbs) to AnAPN1, including mAb 4H5B7, which effectively blocks transmission of natural strains of Plasmodium falciparum. Using the AnAPN1 structure, we map the conformation-dependent 4H5B7 neoepitope to a previously uncharacterized region on domain 1 and further demonstrate that nonhuman-primate neoepitope-specific IgG also blocks parasite transmission. We discuss the prospect of a new biological function of AnAPN1 as a receptor for Plasmodium in the mosquito midgut and the implications for redesigning the AnAPN1 mTBV.

Organizational Affiliation

Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.

Macromolecule Content

Total Structure Weight: 216.47 kDa
Atom Count: 14,305
Modelled Residue Count: 1,777
Deposited Residue Count: 1,922
Unique protein chains: 3

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
AGAP004809-PA	A, B	957	Anopheles gambiae	Mutation(s): 0 Gene Names: AgaP_AGAP004809
UniProt
Find proteins for Q7Q2T8 (Anopheles gambiae) Explore Q7Q2T8 Go to UniProtKB: Q7Q2T8
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q7Q2T8
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
ALA-ALA-ALA-LYS-ALA	C [auth M]	5	Drosophila	Mutation(s): 0
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
ALA-ALA-LYS	D [auth N]	3	Drosophila	Mutation(s): 0
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NHE Query on NHE Download Ideal Coordinates CCD File SDF format, chain H [auth A] MOL2 format, chain H [auth A]	H [auth A]	2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID C₈ H₁₇ N O₃ S MKWKNSIESPFAQN-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Interactions & Density Focus chain H [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain J [auth B] SDF format, chain K [auth B] SDF format, chain L [auth B] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B]	F [auth A], G [auth A], J [auth B], K [auth B], L [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain L [auth B] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain J [auth B] Focus chain K [auth B] Focus chain L [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain I [auth B] MOL2 format, chain E [auth A] MOL2 format, chain I [auth B]	E [auth A], I [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain I [auth B] Interactions & Density Focus chain E [auth A] Focus chain I [auth B]
CU Query on CU Download Ideal Coordinates CCD File SDF format, chain M [auth B] MOL2 format, chain M [auth B]	M [auth B]	COPPER (II) ION Cu JPVYNHNXODAKFH-UHFFFAOYSA-N		Interactions Focus chain M [auth B] Interactions & Density Focus chain M [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.65 Å
R-Value Free: 0.254
R-Value Work: 0.200
R-Value Observed: 0.203
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 113.48	α = 90
b = 132.9	β = 90
c = 146.01	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
MOSFLM	data reduction
SCALA	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2015-06-17

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2015-06-17
Type: Initial release
Version 1.1: 2015-07-01
Changes: Database references
Version 1.2: 2015-07-15
Changes: Database references
Version 1.3: 2023-09-27
Changes: Data collection, Database references, Derived calculations, Refinement description, Source and taxonomy, Structure summary