2p6f

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spinqualitylabelsall models 2p6f, resolution 3.100Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoyl-CoA and inhibitors

Overview

Protein N-myristoylation catalyzed by myristoyl-CoA:protein, N-myristoyltransferase (NMT) plays an important role in a variety of, critical cellular processes and thus is an attractive target for, development of antifungal drugs. We report here three crystal structures, of Saccharomyces. cerevisiae NMT; as a binary complex with myristoyl-CoA, alone and two ternary complexes involving myristoyl-CoA and two different, non-peptidic inhibitors. In all three structures, the majority of the, N-terminal region, absent in all previously reported structures, forms a, well defined motif that is located in the vicinity of the peptide, substrate binding site and is involved in the binding of myristoyl-CoA., The Ab loop, which might be involved in substrate recognition, adopts an, open conformation; while a loop of the N-terminal region (residues 22-24), that covers the top of the substrate binding site, is in the position, occupied by the Ab loop when in the closed conformation. Structural, comparisons with other NMTs, together with mutagenesis data suggest that, the N-terminal region of NMT plays an important role in the binding of, both myristoyl-CoA and peptide substrate, but not in subsequent steps of, the catalytic mechanism. The two inhibitors are found occupying the, peptide substrate binding site and interact with the protein through, primarily hydrophobic contacts. Analyses of the inhibitor-enzyme, interactions provide valuable information for further improvement of, antifungal inhibitors targeting NMT.

About this Structure

2P6F is a Single protein structure of sequence from Saccharomyces cerevisiae with MYA and GN8 as ligands. Active as Glycylpeptide N-tetradecanoyltransferase, with EC number 2.3.1.97 Full crystallographic information is available from OCA.

Reference

Crystal structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoyl-CoA and inhibitors reveal the functional roles of the N-terminal region., Wu J, Tao Y, Zhang M, Howard M, Gutteridge S, Ding J, J Biol Chem. 2007 May 18;. PMID:17513302

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