4C7I

Leismania major N-myristoyltransferase in complex with a peptidomimetic (-OH) molecule

PDB DOI: https://doi.org/10.2210/pdb4C7I/pdb

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

Deposited: 2013-09-20 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: 1.30 Å
R-Value Free: 0.199
R-Value Work: 0.168
R-Value Observed: 0.169

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: 49.18 kDa
Atom Count: 4,348
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 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]
JJ1 Query on JJ1 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]	N-[(1S)-1-{[(1S)-5-AMINO-1-[(2-CYCLOHEXYLETHYL)CARBAMOYL]PENTYL]CARBAMOYL}-2-HYDROXYETHYL]-10-HYDROXYDECANAMIDE C₂₇ H₅₂ N₄ O₅ WOFDCVFMMXKBIZ-ZEQRLZLVSA-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] SDF format, chain F [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A]	E [auth A], F [auth A]	DIMETHYL SULFOXIDE C₂ H₆ O S IAZDPXIOMUYVGZ-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Interactions & Density Focus chain E [auth A] Focus chain F [auth A]
MG Query on MG 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]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.30 Å
R-Value Free: 0.199
R-Value Work: 0.168
R-Value Observed: 0.169
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 48.641	α = 90
b = 91.056	β = 113.98
c = 53.596	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