5G20

Leishmania major N-myristoyltransferase in complex with a quinoline inhibitor (compound 19).

PDB DOI: https://doi.org/10.2210/pdb5G20/pdb

Classification: TRANSFERASE
Organism(s): Leishmania major
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: 1.52 Å
R-Value Free: 0.219
R-Value Work: 0.174
R-Value Observed: 0.176

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: 49 kDa
Atom Count: 3,990
Modelled Residue Count: 411
Deposited Residue Count: 411
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	411	Leishmania major	Mutation(s): 0 EC: 2.3.1.97
UniProt
Find proteins for Q4Q5S8 (Leishmania major) Explore Q4Q5S8 Go to UniProtKB: Q4Q5S8
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q4Q5S8
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
MYA Query on MYA Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	TETRADECANOYL-COA C₃₅ H₆₂ N₇ O₁₇ P₃ S DUAFKXOFBZQTQE-QSGBVPJFSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
QBY Query on QBY 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]	6-(BENZYLOXY)-4-(ETHYLSULFANYL)-3-[(MORPHOLIN-4-YL) C₂₃ H₂₄ N₂ O₃ S INDSTSRQMXNXSG-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
DMS Query on DMS Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.52 Å
R-Value Free: 0.219
R-Value Work: 0.174
R-Value Observed: 0.176
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 47.718	α = 90
b = 90.651	β = 112.72
c = 52.913	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: 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