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spinqualitylabelsall models 1yk3, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of Rv1347c from Mycobacterium tuberculosis

Overview

Mycobacterium tuberculosis, the cause of tuberculosis, is a devastating, human pathogen. The emergence of multidrug resistance in recent years has, prompted a search for new drug targets and for a better understanding of, mechanisms of resistance. Here we focus on the gene product of an open, reading frame from M. tuberculosis, Rv1347c, which is annotated as a, putative aminoglycoside N-acetyltransferase. The Rv1347c protein does not, show this activity, however, and we show from its crystal structure, coupled with functional and bioinformatic data, that its most likely role, is in the biosynthesis of mycobactin, the M. tuberculosis siderophore. The, crystal structure of Rv1347c was determined by multiwavelength anomalous, diffraction phasing from selenomethionine-substituted protein and refined, at 2.2 angstrom resolution (r = 0.227, R(free) = 0.257). The protein is, monomeric, with a fold that places it in the GCN5-related, N-acetyltransferase (GNAT) family of acyltransferases. Features of the, structure are an acyl-CoA binding site that is shared with other GNAT, family members and an adjacent hydrophobic channel leading to the surface, that could accommodate long-chain acyl groups. Modeling the postulated, substrate, the N(epsilon)-hydroxylysine side chain of mycobactin, into the, acceptor substrate binding groove identifies two residues at the active, site, His130 and Asp168, that have putative roles in substrate binding and, catalysis.

About this Structure

1YK3 is a Single protein structure of sequence from Mycobacterium tuberculosis with BOG as ligand. Full crystallographic information is available from OCA.

Reference

The crystal structure of Rv1347c, a putative antibiotic resistance protein from Mycobacterium tuberculosis, reveals a GCN5-related fold and suggests an alternative function in siderophore biosynthesis., Card GL, Peterson NA, Smith CA, Rupp B, Schick BM, Baker EN, J Biol Chem. 2005 Apr 8;280(14):13978-86. Epub 2005 Jan 28. PMID:15695811

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