4FGZ

Crystal Structure of Phosphoethanolamine Methyltransferase from Plasmodium falciparum in Complex with Amodiaquine

PDB DOI: https://doi.org/10.2210/pdb4FGZ/pdb

Classification: TRANSFERASE
Organism(s): Plasmodium falciparum
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2012-06-05 Released: 2012-07-25
Deposition Author(s): Lee, S.G., Alpert, T.D., Jez, J.M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.99 Å
R-Value Free: 0.227
R-Value Work: 0.181
R-Value Observed: 0.183

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This is version 1.2 of the entry. See complete history.

Literature

Crystal structure of phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with amodiaquine.

Lee, S.G., Alpert, T.D., Jez, J.M.

(2012) Bioorg Med Chem Lett 22: 4990-4993

PubMed: 22771008 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1016/j.bmcl.2012.06.032
Primary Citation of Related Structures:
4FGZ

PubMed Abstract:
Phosphoethanolamine N-methyltransferase (PMT) is essential for phospholipid biogenesis in the malarial parasite Plasmodium falciparum. PfPMT catalyzes the triple methylation of phosphoethanolamine to produce phosphocholine, which is then used for phosphatidylcholine synthesis. Here we describe the 2.0Å resolution X-ray crystal structure of PfPMT in complex with amodiaquine. To better characterize inhibition of PfPMT by amodiaquine, we determined the IC(50) values of a series of aminoquinolines using a direct radiochemical assay. Both structural and functional analyses provide a possible approach for the development of new small molecule inhibitors of PfPMT.

Organizational Affiliation

Department of Biology, Washington University, St. Louis, MO 63130, USA.

Macromolecule Content

Total Structure Weight: 64.55 kDa
Atom Count: 4,610
Modelled Residue Count: 516
Deposited Residue Count: 532
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Phosphoethanolamine N-methyltransferase	A, B	266	Plasmodium falciparum	Mutation(s): 0 Gene Names: PMT EC: 2.1.1.103
UniProt
Find proteins for Q8IDQ9 (Plasmodium falciparum (isolate 3D7)) Explore Q8IDQ9 Go to UniProtKB: Q8IDQ9
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q8IDQ9
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SAH Query on SAH 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]	S-ADENOSYL-L-HOMOCYSTEINE C₁₄ H₂₀ N₆ O₅ S ZJUKTBDSGOFHSH-WFMPWKQPSA-N		Interactions Focus chain E [auth A] Focus chain I [auth B] Interactions & Density Focus chain E [auth A] Focus chain I [auth B]
CQA Query on CQA Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B]	C [auth A], D [auth A], G [auth B], H [auth B]	4-[(7-CHLOROQUINOLIN-4-YL)AMINO]-2-[(DIETHYLAMINO)METHYL]PHENOL C₂₀ H₂₂ Cl N₃ O OVCDSSHSILBFBN-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain G [auth B] Focus chain H [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain G [auth B] Focus chain H [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain J [auth B] MOL2 format, chain F [auth A] MOL2 format, chain J [auth B]	F [auth A], J [auth B]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain F [auth A] Focus chain J [auth B] Interactions & Density Focus chain F [auth A] Focus chain J [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
CQA	Binding MOAD: 4FGZ	IC50: 1.35e+6 (nM) from 1 assay(s)
	BindingDB: 4FGZ	IC50: 1.35e+6 (nM) from 1 assay(s)
	PDBBind: 4FGZ	IC50: 1.35e+6 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.99 Å
R-Value Free: 0.227
R-Value Work: 0.181
R-Value Observed: 0.183
Space Group: P 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 66.051	α = 90
b = 60.639	β = 90.008
c = 68.151	γ = 90

Software Package:

Software Name	Purpose
HKL-3000	data collection
PHASER	phasing
PHENIX	refinement
HKL-3000	data reduction
HKL-3000	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-07-25

Deposition Author(s):

Lee, S.G.

Alpert, T.D.

Jez, J.M.

Revision History (Full details and data files)

Version 1.0: 2012-07-25
Type: Initial release
Version 1.1: 2012-08-01
Changes: Database references
Version 1.2: 2024-02-28
Changes: Data collection, Database references, Derived calculations, Structure summary