Take our Survey

Reference: Wu J, et al. (2007) Crystal Structures of Saccharomyces cerevisiae N-Myristoyltransferase with Bound Myristoyl-CoA and Inhibitors Reveal the Functional Roles of the N-terminal Region. J Biol Chem 282(30):22185-94

Reference Help

Abstract


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.

Reference Type
Journal Article
Authors
Wu J, Tao Y, Zhang M, Howard M, Gutteridge S, Ding J
Primary Lit For
Additional Lit For
Review For

Interaction Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference