PDBsum entry: 1iyl

Transferase

PDB id: 1iyl

Contents

Protein chains

384 a.a. *

Ligands

R64 ×3

* Residue conservation analysis

PDB id:

1iyl

Name:

Transferase

Title:

Crystal structure of candida albicans n-myristoyltransferase peptidic inhibitor

Structure:

Myristoyl-coa:protein n-myristoyltransferase. Chain: a, b, c, d. Synonym: glycylpeptide n-tetradecanoyltransferase. Engineered: yes

Source:

Candida albicans. Organism_taxid: 5476. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

3.20Å R-factor: 0.288 R-free: 0.366

Authors:

S.Sogabe,T.A.Fukami,K.Morikami,Y.Shiratori,Y.Aoki,A.D'Arcy, F.K.Winkler,D.W.Banner,T.Ohtsuka

Key ref:

S.Sogabe et al. (2002). Crystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors. Chem Biol, 9, 1119-1128. PubMed id: 12401496 DOI: 10.1016/S1074-5521(02)00240-5

Date:

29-Aug-02 Release date: 30-Dec-02

Protein chains

P30418  (NMT_CANAL) -  Glycylpeptide N-tetradecanoyltransferase

Seq: 451 a.a.

Struc: 384 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.97 - Glycylpeptide N-tetradecanoyltransferase.
• Reaction: Tetradecanoyl-CoA + glycylpeptide = CoA + N-tetradecanoylglycylpeptide

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

 Gene Ontology (GO) functional annotation 

• Biological process: N-terminal protein myristoylation (1 term)
• Biochemical function: glycylpeptide N-tetradecanoyltransferase activity (1 term)

reference

DOI no: 10.1016/S1074-5521(02)00240-5

Chem Biol 9:1119-1128 (2002)

PubMed id: 12401496

Crystal structures of Candida albicans N-myristoyltransferase with two distinct inhibitors.

S.Sogabe, M.Masubuchi, K.Sakata, T.A.Fukami, K.Morikami, Y.Shiratori, H.Ebiike, K.Kawasaki, Y.Aoki, N.Shimma, A.D'Arcy, F.K.Winkler, D.W.Banner, T.Ohtsuka.

ABSTRACT

Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme that catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. Genetic and biochemical studies have established that Nmt is an attractive target for antifungal drugs. We present here crystal structures of C. albicans Nmt complexed with two classes of inhibitor competitive for peptide substrates. One is a peptidic inhibitor designed from the peptide substrate; the other is a nonpeptidic inhibitor having a benzofuran core. Both inhibitors are bound into the same binding groove, generated by some structural rearrangements of the enzyme, with the peptidic inhibitor showing a substrate-like binding mode and the nonpeptidic inhibitor binding differently. Further, site-directed mutagenesis for C. albicans Nmt has been utilized in order to define explicitly which amino acids are critical for inhibitor binding. The results suggest that the enzyme has some degree of flexibility for substrate binding and provide valuable information for inhibitor design.

Selected figure(s)

Figure 1.
Figure 1. Ribbon Model of C. albicans Nmt in Complex with Myristoyl-CoA and SC-58272Myristoyl-CoA and SC-58272 is shown as a stick model. Color codes of atoms are as follows: oxygen atoms, red; nitrogen atoms, blue; carbon atoms, gray.

Figure 2.
Figure 2. The Binding Mode of the InhibitorsThe inhibitors SC-58272 (A) and compound 5 (B) are outlined by the σ[A]-weighted Fo-Fc electron density map at the 3σ level with final model of the protein. Atoms are colored as in Figure 1, except that carbon atoms of the protein and the inhibitor are gray and yellow, respectively. Dashed magenta lines indicate hydrogen bond interactions. A schematic drawing of the interactions of compound 5 is shown in (C).

The above figures are reprinted by permission from Cell Press: Chem Biol (2002, 9, 1119-1128) copyright 2002.

Figures were selected by an automated process.