Reference: Parsons L, et al. (2003) Solution structure and functional ligand screening of HI0719, a highly conserved protein from bacteria to humans in the YjgF/YER057c/UK114 family. Biochemistry 42(1):80-9

Reference Help

Abstract


HI0719 belongs to a large family of highly conserved proteins with no definitive molecular function and is found in organisms ranging from bacteria to humans. We describe the NMR structure of HI0719, the first solution structure for a member of this family. The overall fold is similar to the crystal structures of two homologues, YabJ from Bacillus subtilis and YjgF from Escherichia coli, and all three structures are similar to that of chorismate mutase, although there is little sequence homology and no apparent functional connection. HI0719 is a homotrimer with a distinct cavity located at the subunit interface. Six of the seven invariant residues in the high identity group of proteins are located in this cavity, suggesting that this may be a binding site for small molecules. Using previously published observations about the biological role of HI0719 family members as a guide, over 100 naturally occurring small molecules or structural analogues were screened for ligand binding using NMR spectroscopy. The targeted screening approach identified six compounds that bind to HI0719 at the putative active site. Five of these compounds are either alpha-keto acids or alpha,beta-unsaturated acids, while the sixth compound is structurally similar. Previous studies have proposed that some HI0719 homologues may act on small molecules in the isoleucine biosynthetic path and, if this is correct, the ligand screening results presented here suggest that the interaction most likely occurs with 2-ketobutyrate and/or its unstable enamine precursor.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.
Authors
Parsons L, Bonander N, Eisenstein E, Gilson M, Kairys V, Orban 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