PDBsum entry 4ucn

Transferase

PDB id: 4ucn

Contents

Protein chain

411 a.a.

Ligands

JRB

MYA

Waters ×324

PDB id:

4ucn

Name:

Transferase

Title:

Crystal structure of leishmania major n-myristoyltransferase (nmt) with bound myristoyl-coa and a fragment

Structure:

Glycylpeptide n-tetradecanoyltransferase. Chain: a. Fragment: residues 5-421. Engineered: yes

Source:

Leishmania major. Organism_taxid: 5664. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.80Å R-factor: 0.170 R-free: 0.200

Authors:

D.A.Robinson,P.G.Wyatt

Key ref:

D.A.Robinson and P.G.Wyatt (2015). Identification and structure solution of fragment hits against kinetoplastid N-myristoyltransferase. Acta Crystallogr F Struct Biol Commun, 71, 586-593. PubMed id: 25945713 DOI: 10.1107/S2053230X15003040

Date:

04-Dec-14 Release date: 13-May-15

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

DOI no: 10.1107/S2053230X15003040

Acta Crystallogr F Struct Biol Commun 71:586-593 (2015)

PubMed id: 25945713

Identification and structure solution of fragment hits against kinetoplastid N-myristoyltransferase.

D.A.Robinson, P.G.Wyatt.

ABSTRACT

Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis. Pyrazole sulfonamide (DDD85646), a potent inhibitor of TbNMT, has been identified in previous studies; however, poor central nervous system exposure restricts its use to the haemolymphatic form (stage 1) of the disease. In order to identify new chemical matter, a fragment screen was carried out by ligand-observed NMR spectroscopy, identifying hits that occupy the DDD85646 binding site. Crystal structures of hits from this assay have been obtained in complex with the closely related NMT from Leishmania major, providing a structural starting point for the evolution of novel chemical matter.