5A28

Leishmania major N-myristoyltransferase in complex with a chlorophenyl 1,3,4-oxadiazole inhibitor.

PDB DOI: https://doi.org/10.2210/pdb5A28/pdb

Classification: TRANSFERASE
Organism(s): Leishmania major
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2015-05-15 Released: 2016-03-23
Deposition Author(s): Rackham, M.D., Yu, Z., Brannigan, J.A., Heal, W.P., Paape, D., Barker, K.V., Wilkinson, A.J., Smith, D.F., Tate, E.W., Leatherbarrow, R.J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.48 Å
R-Value Free: 0.245
R-Value Work: 0.201
R-Value Observed: 0.203

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Discovery of High Affinity Inhibitors of Leishmania Donovani N-Myristoyltransferase.

Rackham, M.D., Yu, Z., Brannigan, J.A., Heal, W.P., Paape, D., Barker, K.V., Wilkinson, A.J., Smith, D.F., Leatherbarrow, R.J., Tate, E.W.

(2015) Medchemcomm 6: 1761

PubMed: 26962429 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1039/c5md00241a
Primary Citation of Related Structures:
5A27, 5A28

PubMed Abstract:
N -Myristoyltransferase (NMT) is a potential drug target in Leishmania parasites. Scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for Leishmania donovani NMT; development led to high affinity inhibitors with excellent ligand efficiency. The binding mode was characterised by crystallography and provides a structural rationale for selectivity.

Organizational Affiliation

Department of Chemistry , Imperial College London , South Kensington Campus , London , SW7 2AZ , UK . Email: [email protected] ; Tel: +44 (0) 2075 943752.

Macromolecule Content

Total Structure Weight: 48.91 kDa
Atom Count: 4,018
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 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
MYA Query on MYA 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]	TETRADECANOYL-COA C₃₅ H₆₂ N₇ O₁₇ P₃ S DUAFKXOFBZQTQE-QSGBVPJFSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
TUQ Query on TUQ 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]	4-(4-chloro-2-{5-[(trimethyl-1H-pyrazol-4-yl)methyl]-1,3,4-oxadiazol-2-yl}phenoxy)piperidine C₂₀ H₂₄ Cl N₅ O₂ AYWNZLSZEHOECC-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
MG Query on MG 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]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
TUQ	BindingDB: 5A28	Ki: 25 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.48 Å
R-Value Free: 0.245
R-Value Work: 0.201
R-Value Observed: 0.203
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 48.447	α = 90
b = 92.161	β = 113.79
c = 53.461	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: 2016-03-23

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2016-03-23
Type: Initial release
Version 1.1: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Other