PDBsum entry 5t6h

Transferase

PDB id: 5t6h

Contents

Protein chain

392 a.a.

Ligands

MYA

75Q

Waters ×514

PDB id:

5t6h

Name:

Transferase

Title:

Crystal structure of aspergillus fumigatus n-myristoyl transferase in complex with myristoyl coa and a dimethylpyridyl-dipihenyl-pyridine ligand

Structure:

Glycylpeptide n-tetradecanoyltransferase. Chain: a. Synonym: myristoyl-coa:protein n-myristoyltransferase,nmt,peptide n- myristoyltransferase. Engineered: yes

Source:

Neosartorya fumigata (strain atcc mya-4609 / af293 / cbs 101355 / fgsc a1100). Organism_taxid: 330879. Strain: atcc mya-4609 / af293 / cbs 101355 / fgsc a1100. Gene: nmt1, afua_4g08070. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss.

Resolution:

1.80Å R-factor: 0.175 R-free: 0.213

Authors:

D.A.Robinson,P.G.Wyatt

Key ref:

T.Bayliss et al. (2017). Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors. J Med Chem, 60, 9790-9806. PubMed id: 29125744

Date:

01-Sep-16 Release date: 13-Sep-17

Protein chain

Q9UVX3  (NMT_ASPFU) -  Glycylpeptide N-tetradecanoyltransferase from Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293)

Seq: 492 a.a.

Struc: 392 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

J Med Chem 60:9790-9806 (2017)

PubMed id: 29125744

Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors.

T.Bayliss, D.A.Robinson, V.C.Smith, S.Brand, S.P.McElroy, L.S.Torrie, C.Mpamhanga, S.Norval, L.Stojanovski, R.Brenk, J.A.Frearson, K.D.Read, I.H.Gilbert, P.G.Wyatt.

ABSTRACT

N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.