4KRG

SeMet Haemonchus contortus Phosphoethanolamine N-methyltransferase 1 in complex with phosphoethanolamine and S-adenosylhomocysteine

PDB DOI: https://doi.org/10.2210/pdb4KRG/pdb

Classification: TRANSFERASE
Organism(s): Haemonchus contortus
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2013-05-16 Released: 2013-09-25
Deposition Author(s): Lee, S.G., Jez, J.M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.68 Å
R-Value Free: 0.140
R-Value Work: 0.121
R-Value Observed: 0.123

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Evolution of structure and mechanistic divergence in di-domain methyltransferases from nematode phosphocholine biosynthesis.

Lee, S.G., Jez, J.M.

(2013) Structure 21: 1778-1787

PubMed: 24012478 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1016/j.str.2013.07.023
Primary Citation of Related Structures:
4KRG, 4KRH, 4KRI

PubMed Abstract:
The phosphobase methylation pathway is the major route for supplying phosphocholine to phospholipid biosynthesis in plants, nematodes, and Plasmodium. In this pathway, phosphoethanolamine N-methyltransferase (PMT) catalyzes the sequential methylation of phosphoethanolamine to phosphocholine. In the PMT, one domain (MT1) catalyzes methylation of phosphoethanolamine to phosphomonomethylethanolamine and a second domain (MT2) completes the synthesis of phosphocholine. The X-ray crystal structures of the di-domain PMT from the parasitic nematode Haemonchus contortus (HcPMT1 and HcPMT2) reveal that the catalytic domains of these proteins are structurally distinct and allow for selective methylation of phosphobase substrates using different active site architectures. These structures also reveal changes leading to loss of function in the vestigial domains of the nematode PMT. Divergence of function in the two nematode PMTs provides two distinct antiparasitic inhibitor targets within the same essential metabolic pathway. The PMTs from nematodes, plants, and Plasmodium also highlight adaptable metabolic modularity in evolutionarily diverse organisms.

Organizational Affiliation

Department of Biology, Washington University in St. Louis, One Brookings Drive, Campus Box 1137, St. Louis, MO 63130, USA.

Macromolecule Content

Total Structure Weight: 111.23 kDa
Atom Count: 9,786
Modelled Residue Count: 932
Deposited Residue Count: 932
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Phosphoethanolamine N-methyltransferase 1	A, B	466	Haemonchus contortus	Mutation(s): 0
UniProt
Find proteins for U5HK46 (Haemonchus contortus) Explore U5HK46 Go to UniProtKB: U5HK46
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	U5HK46
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SAH Query on SAH Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain I [auth B] MOL2 format, chain D [auth A] MOL2 format, chain I [auth B]	D [auth A], I [auth B]	S-ADENOSYL-L-HOMOCYSTEINE C₁₄ H₂₀ N₆ O₅ S ZJUKTBDSGOFHSH-WFMPWKQPSA-N		Interactions Focus chain D [auth A] Focus chain I [auth B] Interactions & Density Focus chain D [auth A] Focus chain I [auth B]
BOG Query on BOG Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain J [auth B] SDF format, chain K [auth B] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B]	E [auth A], F [auth A], J [auth B], K [auth B]	octyl beta-D-glucopyranoside C₁₄ H₂₈ O₆ HEGSGKPQLMEBJL-RKQHYHRCSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain J [auth B] Focus chain K [auth B] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain J [auth B] Focus chain K [auth B]
OPE Query on OPE Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain C [auth A] MOL2 format, chain H [auth B] MOL2 format, chain C [auth A]	C [auth A], H [auth B]	PHOSPHORIC ACID MONO-(2-AMINO-ETHYL) ESTER C₂ H₈ N O₄ P SUHOOTKUPISOBE-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain H [auth B] Interactions & Density Focus chain C [auth A] Focus chain H [auth B]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain L [auth B] MOL2 format, chain G [auth A] MOL2 format, chain L [auth B]	G [auth A], L [auth B]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain L [auth B] Interactions & Density Focus chain G [auth A] Focus chain L [auth B]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
MSE Query on MSE	A, B	L-PEPTIDE LINKING	C₅ H₁₁ N O₂ Se		MET

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.68 Å
R-Value Free: 0.140
R-Value Work: 0.121
R-Value Observed: 0.123
Space Group: P 6₅

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 72.998	α = 90
b = 72.998	β = 90
c = 360.62	γ = 120

Software Package:

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

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2013-09-25

Deposition Author(s):

Lee, S.G.

Jez, J.M.

Revision History (Full details and data files)

Version 1.0: 2013-09-25
Type: Initial release
Version 1.1: 2013-10-30
Changes: Database references
Version 1.2: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Data collection, Derived calculations, Structure summary