5G1Z

Plasmodium vivax N-myristoyltransferase in complex with a quinoline inhibitor (compound 1)

PDB DOI: https://doi.org/10.2210/pdb5G1Z/pdb

Classification: TRANSFERASE
Organism(s): Plasmodium vivax
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2016-04-06 Released: 2017-02-15
Deposition Author(s): Goncalves, V., Brannigan, J.A., Laporte, A., Bell, A.S., Roberts, S.M., Wilkinson, A.J., Leatherbarrow, R.J., Tate, E.W.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.50 Å
R-Value Free: 0.187
R-Value Work: 0.149
R-Value Observed: 0.151

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Structure-guided optimization of quinoline inhibitors of Plasmodium N-myristoyltransferase.

Goncalves, V., Brannigan, J.A., Laporte, A., Bell, A.S., Roberts, S.M., Wilkinson, A.J., Leatherbarrow, R.J., Tate, E.W.

(2017) Medchemcomm 8: 191-197

PubMed: 28626547 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1039/c6md00531d
Primary Citation of Related Structures:
5G1Z, 5G20, 5G21, 5G22

PubMed Abstract:
The parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N -Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both Plasmodium vivax and Plasmodium falciparum N -myristoyltransferase (NMT).

Organizational Affiliation

Department of Chemistry , Imperial College London , London SW7 2AZ , UK . Email: [email protected] ; Email: [email protected].

Macromolecule Content

Total Structure Weight: 139.79 kDa
Atom Count: 11,889
Modelled Residue Count: 1,140
Deposited Residue Count: 1,155
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
GLYCYLPEPTIDE N-TETRADECANOYLTRANSFERASE	A, B, C	385	Plasmodium vivax	Mutation(s): 0 EC: 2.3.1.97
UniProt
Find proteins for A5K1A2 (Plasmodium vivax (strain Salvador I)) Explore A5K1A2 Go to UniProtKB: A5K1A2
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	A5K1A2
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 6 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NHW Query on NHW Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain K [auth B] SDF format, chain P [auth C] MOL2 format, chain D [auth A] MOL2 format, chain K [auth B] MOL2 format, chain P [auth C] mmCIF format, chain D [auth A] mmCIF format, chain K [auth B] mmCIF format, chain P [auth C]	D [auth A], K [auth B], P [auth C]	2-oxopentadecyl-CoA C₃₆ H₆₄ N₇ O₁₇ P₃ S JKWHUJMJVNMKEF-UOCZADIYSA-J		Interactions Focus chain D [auth A] Focus chain K [auth B] Focus chain P [auth C] Interactions & Density Focus chain D [auth A] Focus chain K [auth B] Focus chain P [auth C]
U53 Query on U53 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain L [auth B] SDF format, chain Q [auth C] MOL2 format, chain E [auth A] MOL2 format, chain L [auth B] MOL2 format, chain Q [auth C] mmCIF format, chain E [auth A] mmCIF format, chain L [auth B] mmCIF format, chain Q [auth C]	E [auth A], L [auth B], Q [auth C]	ethyl 4-(2-cyanoethylsulfanyl)-6-methoxy-quinoline-3-carboxylate C₁₆ H₁₆ N₂ O₃ S TZDUQSHGGUOAJU-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain L [auth B] Focus chain Q [auth C] Interactions & Density Focus chain E [auth A] Focus chain L [auth B] Focus chain Q [auth C]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain I [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A]	H [auth A], I [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain H [auth A] Focus chain I [auth A] Interactions & Density Focus chain H [auth A] Focus chain I [auth A]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain M [auth B] SDF format, chain R [auth C] SDF format, chain S [auth C] MOL2 format, chain F [auth A] MOL2 format, chain M [auth B] MOL2 format, chain R [auth C] MOL2 format, chain S [auth C] mmCIF format, chain F [auth A] mmCIF format, chain M [auth B] mmCIF format, chain R [auth C] mmCIF format, chain S [auth C]	F [auth A], M [auth B], R [auth C], S [auth C]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain M [auth B] Focus chain R [auth C] Focus chain S [auth C] Interactions & Density Focus chain F [auth A] Focus chain M [auth B] Focus chain R [auth C] Focus chain S [auth C]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain J [auth A] SDF format, chain O [auth B] SDF format, chain U [auth C] MOL2 format, chain J [auth A] MOL2 format, chain O [auth B] MOL2 format, chain U [auth C] mmCIF format, chain J [auth A] mmCIF format, chain O [auth B] mmCIF format, chain U [auth C]	J [auth A], O [auth B], U [auth C]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain J [auth A] Focus chain O [auth B] Focus chain U [auth C] Interactions & Density Focus chain J [auth A] Focus chain O [auth B] Focus chain U [auth C]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain N [auth B] SDF format, chain T [auth C] MOL2 format, chain G [auth A] MOL2 format, chain N [auth B] MOL2 format, chain T [auth C] mmCIF format, chain G [auth A] mmCIF format, chain N [auth B] mmCIF format, chain T [auth C]	G [auth A], N [auth B], T [auth C]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain N [auth B] Focus chain T [auth C] Interactions & Density Focus chain G [auth A] Focus chain N [auth B] Focus chain T [auth C]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.50 Å
R-Value Free: 0.187
R-Value Work: 0.149
R-Value Observed: 0.151
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 57.4	α = 90
b = 118.9	β = 90
c = 175.3	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
SCALA	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2017-02-15

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2017-02-15
Type: Initial release
Version 1.1: 2017-06-28
Changes: Database references
Version 1.2: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Other