PDBsum entry 4c7h

Transferase

PDB id: 4c7h

Contents

Protein chain

411 a.a.

Ligands

EN5

COA-MYA-ENF

DMS ×2

Metals

_MG

Waters ×540

PDB id:

4c7h

Name:

Transferase

Title:

Leismania major n-myristoyltransferase in complex with a peptidomimetic (-nh2) molecule

Structure:

Glycylpeptide n-tetradecanoyltransferase. Chain: a. Fragment: residues 11-421. Engineered: yes

Source:

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

Resolution:

1.40Å R-factor: 0.174 R-free: 0.205

Authors:

T.O.Olaleye,J.A.Brannigan,V.Goncalves,S.M.Roberts,R.J.Leatherbarrow, A.J.Wilkinson,E.W.Tate

Key ref:

T.O.Olaleye et al. (2014). Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites. Org Biomol Chem, 12, 8132-8137. PubMed id: 25230674 DOI: 10.1039/c4ob01669f

Date:

20-Sep-13 Release date: 24-Sep-14

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] (Bound ligand (Het Group name = COA) corresponds exactly) + CoA + H(+)

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

Added reference

DOI no: 10.1039/c4ob01669f

Org Biomol Chem 12:8132-8137 (2014)

PubMed id: 25230674

Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites.

T.O.Olaleye, J.A.Brannigan, S.M.Roberts, R.J.Leatherbarrow, A.J.Wilkinson, E.W.Tate.

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.