PDBsum entry 5g21

Transferase

PDB id: 5g21

Contents

Protein chain

411 a.a.

Ligands

MYA

YN4

Metals

_MG

Waters ×376

PDB id:

5g21

Name:

Transferase

Title:

Leishmania major n-myristoyltransferase in complex with a quinoline inhibitor (compound 26).

Structure:

Glycylpeptide n-tetradecanoyltransferase. Chain: a. Engineered: yes

Source:

Leishmania major. Organism_taxid: 5664. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta2 plyss.

Resolution:

1.50Å R-factor: 0.176 R-free: 0.209

Authors:

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

Key ref:

V.Goncalves et al. (2017). Structure-guided optimization of quinoline inhibitors ofPlasmodium N-myristoyltransferase. Medchemcomm, 8, 191-197. PubMed id: 28626547

Date:

06-Apr-16 Release date: 15-Feb-17

Protein chain

Q4Q5S8  (Q4Q5S8_LEIMA) -  Glycylpeptide N-tetradecanoyltransferase from Leishmania major

Seq: 421 a.a.

Struc: 411 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.97 - glycylpeptide N-tetradecanoyltransferase.
• Reaction: N-terminal glycyl-[protein] + tetradecanoyl-CoA = N-tetradecanoylglycyl- [protein] + CoA + H⁺

N-terminal glycyl-[protein] + tetradecanoyl-CoA (Bound ligand (Het Group name = MYA) corresponds exactly) = N-tetradecanoylglycyl- [protein] + CoA + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Medchemcomm 8:191-197 (2017)

PubMed id: 28626547

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

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

ABSTRACT

The parasitePlasmodium vivaxis 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 bothPlasmodium vivaxandPlasmodium falciparum N-myristoyltransferase (NMT).