4rx1

Crystal Structure of antibiotic-resistance methyltransferase Kmr

spinqualitylabelsall models 4rx1, resolution 2.47Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rx1 is a 2 chain structure with sequence from "polyangium_compositum"_thaxter_1904 "polyangium compositum" thaxter 1904. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, IOD Related: 4rwz Gene: kmr ("Polyangium compositum" Thaxter 1904) Activity: 16S rRNA (guanine(1405)-N(7))-methyltransferase, with EC number 2.1.1.179 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Methylation of bacterial 16S rRNA within the ribosomal decoding center confers exceptionally high resistance to aminoglycoside antibiotics. This resistance mechanism is exploited by aminoglycoside producers for self-protection while functionally equivalent methyltransferases have been acquired by human and animal pathogenic bacteria. Here, we report structural and functional analyses of the Sorangium cellulosum So ce56 aminoglycoside resistance-conferring methyltransferase Kmr. Our results demonstrate that Kmr is a 16S rRNA methyltransferase acting at residue A1408 to confer a canonical aminoglycoside resistance spectrum in Escherichia coli. Kmr possesses a class I methyltransferase core fold but with dramatic differences in the regions which augment this structure to confer substrate specificity in functionally related enzymes. Most strikingly, the region linking core beta-strands 6 and 7, which forms part of the S-adenosyl-l-methionine (SAM) binding pocket and contributes to base flipping by the m(1)A1408 methyltransferase NpmA, is disordered in Kmr, correlating with an exceptionally weak affinity for SAM. Kmr is unexpectedly insensitive to substitutions of residues critical for activity of other 16S rRNA (A1408) methyltransferases and also to the effects of by-product inhibition by S-adenosylhomocysteine (SAH). Collectively, our results indicate that adoption of a catalytically competent Kmr conformation and binding of the obligatory cosubstrate SAM must be induced by interaction with the 30S subunit substrate. 30S Subunit-Dependent Activation of the Sorangium cellulosum So ce56 Aminoglycoside Resistance-Conferring 16S rRNA Methyltransferase Kmr.,Savic M, Sunita S, Zelinskaya N, Desai PM, Macmaster R, Vinal K, Conn GL Antimicrob Agents Chemother. 2015 May;59(5):2807-16. doi: 10.1128/AAC.00056-15., Epub 2015 Mar 2. PMID:25733511 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA