2hw2 | pdb_00002hw2

Crystal structure of Rifampin ADP-ribosyl transferase in complex with Rifampin

spinqualitylabelsall models 2hw2, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2hw2 is a 1 chain structure with sequence from "bacillus_smegmatis"_trevisan_1889 "bacillus smegmatis" trevisan 1889. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GLY, RFP Gene: arr ("Bacillus smegmatis" Trevisan 1889) Activity: NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The rifamycin antibiotic rifampin is important for the treatment of tuberculosis and infections caused by multidrug-resistant Staphylococcus aureus. Recent iterations of the rifampin core structure have resulted in new drugs and drug candidates for the treatment of a much broader range of infectious diseases. This expanded use of rifamycin antibiotics has the potential to select for increased resistance. One poorly characterized mechanism of resistance is through Arr enzymes that catalyze ADP-ribosylation of rifamycins. We find that genes encoding predicted Arr enzymes are widely distributed in the genomes of pathogenic and nonpathogenic bacteria. Biochemical analysis of three representative Arr enzymes from environmental and pathogenic bacterial sources shows that these have equally efficient drug resistance capacity in vitro and in vivo. The 3D structure of one of these orthologues from Mycobacterium smegmatis was determined and reveals structural homology with ADP-ribosyltransferases important in eukaryotic biology, including poly(ADP-ribose) polymerases (PARPs) and bacterial toxins, despite no significant amino acid sequence homology with these proteins. This work highlights the extent of the rifamycin resistome in microbial genera with the potential to negatively impact the expanded use of this class of antibiotic. Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr.,Baysarowich J, Koteva K, Hughes DW, Ejim L, Griffiths E, Zhang K, Junop M, Wright GD Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4886-91. Epub 2008 Mar 18. PMID:18349144 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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