4C68

Plasmodium vivax N-myristoyltransferase in complex with a peptidomimetic inhibitor

PDB DOI: https://doi.org/10.2210/pdb4C68/pdb

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

Deposited: 2013-09-17 Released: 2014-09-24
Deposition Author(s): Olaleye, T.O., Brannigan, J.A., Goncalves, V., Roberts, S.M., Leatherbarrow, R.J., Wilkinson, A.J., Tate, E.W.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.38 Å
R-Value Free: 0.260
R-Value Work: 0.220
R-Value Observed: 0.222

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Peptidomimetic Inhibitors of N-Myristoyltransferase from Human Malaria and Leishmaniasis Parasites.

Olaleye, T.O., Brannigan, J.A., Roberts, S.M., Leatherbarrow, R.J., Wilkinson, A.J., Tate, E.W.

(2014) Org Biomol Chem 12: 8132

PubMed: 25230674 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1039/c4ob01669f
Primary Citation of Related Structures:
4C68, 4C7H, 4C7I

PubMed Abstract:
N-Myristoyltransferase (NMT) has been shown to be essential in Leishmania and subsequently validated as a drug target in Plasmodium. Herein, we discuss the use of antifungal NMT inhibitors as a basis for inhibitor development resulting in the first sub-micromolar peptidomimetic inhibitors of Plasmodium and Leishmania NMTs. High-resolution structures of these inhibitors with Plasmodium and Leishmania NMTs permit a comparative analysis of binding modes, and provide the first crystal structure evidence for a ternary NMT-Coenzyme A/myristoylated peptide product complex.

Organizational Affiliation

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

Macromolecule Content

Total Structure Weight: 139.62 kDa
Atom Count: 11,510
Modelled Residue Count: 1,138
Deposited Residue Count: 1,152
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	384	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 7 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NHW Query on NHW Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain N [auth B] SDF format, chain S [auth C] MOL2 format, chain G [auth A] MOL2 format, chain N [auth B] MOL2 format, chain S [auth C] mmCIF format, chain G [auth A] mmCIF format, chain N [auth B] mmCIF format, chain S [auth C]	G [auth A], N [auth B], S [auth C]	2-oxopentadecyl-CoA C₃₆ H₆₄ N₇ O₁₇ P₃ S JKWHUJMJVNMKEF-UOCZADIYSA-J		Interactions Focus chain G [auth A] Focus chain N [auth B] Focus chain S [auth C] Interactions & Density Focus chain G [auth A] Focus chain N [auth B] Focus chain S [auth C]
EN5 Query on EN5 Download Ideal Coordinates CCD File SDF format, chain M [auth B] SDF format, chain F [auth A] MOL2 format, chain M [auth B] MOL2 format, chain F [auth A] mmCIF format, chain M [auth B] mmCIF format, chain F [auth A]	F [auth A], M [auth B]	N-(10-aminodecanoyl)-L-seryl-N-(2-cyclohexylethyl)-L-lysinamide C₂₇ H₅₃ N₅ O₄ OVRFOVZVAWIPDE-ZEQRLZLVSA-N		Interactions Focus chain F [auth A] Focus chain M [auth B] Interactions & Density Focus chain F [auth A] Focus chain M [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain J [auth A] MOL2 format, chain J [auth A] mmCIF format, chain J [auth A]	J [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain J [auth A] Interactions & Density Focus chain J [auth A]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain K [auth A] SDF format, chain L [auth B] SDF format, chain Q [auth B] SDF format, chain R [auth C] MOL2 format, chain E [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth B] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth C] mmCIF format, chain E [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth B] mmCIF format, chain Q [auth B] mmCIF format, chain R [auth C]	E [auth A], K [auth A], L [auth B], Q [auth B], R [auth C]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain K [auth A] Focus chain L [auth B] Focus chain Q [auth B] Focus chain R [auth C] Interactions & Density Focus chain E [auth A] Focus chain K [auth A] Focus chain L [auth B] Focus chain Q [auth B] Focus chain R [auth C]
FMT Query on FMT Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A] mmCIF format, chain D [auth A]	D [auth A]	FORMIC ACID C H₂ O₂ BDAGIHXWWSANSR-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain U [auth C] SDF format, chain O [auth B] SDF format, chain T [auth C] SDF format, chain V [auth C] MOL2 format, chain H [auth A] MOL2 format, chain U [auth C] MOL2 format, chain O [auth B] MOL2 format, chain T [auth C] MOL2 format, chain V [auth C] mmCIF format, chain H [auth A] mmCIF format, chain U [auth C] mmCIF format, chain O [auth B] mmCIF format, chain T [auth C] mmCIF format, chain V [auth C]	H [auth A], O [auth B], T [auth C], U [auth C], V [auth C]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain H [auth A] Focus chain O [auth B] Focus chain T [auth C] Focus chain U [auth C] Focus chain V [auth C] Interactions & Density Focus chain H [auth A] Focus chain O [auth B] Focus chain T [auth C] Focus chain U [auth C] Focus chain V [auth C]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain P [auth B] SDF format, chain W [auth C] MOL2 format, chain I [auth A] MOL2 format, chain P [auth B] MOL2 format, chain W [auth C] mmCIF format, chain I [auth A] mmCIF format, chain P [auth B] mmCIF format, chain W [auth C]	I [auth A], P [auth B], W [auth C]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Focus chain P [auth B] Focus chain W [auth C] Interactions & Density Focus chain I [auth A] Focus chain P [auth B] Focus chain W [auth C]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.38 Å
R-Value Free: 0.260
R-Value Work: 0.220
R-Value Observed: 0.222
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 57.33	α = 90
b = 121.43	β = 90
c = 178.74	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
SCALA	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2014-09-24

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2014-09-24
Type: Initial release
Version 1.1: 2014-10-01
Changes: Database references
Version 1.2: 2014-10-08
Changes: Database references
Version 1.3: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Other