3lcu

From Proteopedia

Crystal Structure of Antibiotic related Methyltransferase

Structural highlights

3lcu is a 1 chain structure with sequence from Micromonospora zionensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SGM_MICZI Specifically methylates the N(7) position of guanine 1405 in 16S rRNA. Confers resistance to various aminoglycosides, including gentamicin, kanamycin and sisomicin.^[1] ^[2]

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

Sgm (Sisomicin-gentamicin methyltransferase) from antibiotic-producing bacterium Micromonospora zionensis is an enzyme that confers resistance to aminoglycosides like gentamicin and sisomicin by specifically methylating G1405 in bacterial 16S rRNA. Sgm belongs to the aminoglycoside resistance methyltransferase (Arm) family of enzymes that have been recently found to spread by horizontal gene transfer among disease-causing bacteria. Structural characterization of Arm enzymes is the key to understand their mechanism of action and to develop inhibitors that would block their activity. Here we report the structure of Sgm in complex with cofactors S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) at 2.0 and 2.1 A resolution, respectively, and results of mutagenesis and rRNA footprinting, and protein-substrate docking. We propose the mechanism of methylation of G1405 by Sgm and compare it with other m(7)G methyltransferases, revealing a surprising diversity of active sites and binding modes for the same basic reaction of RNA modification. This analysis can serve as a stepping stone towards developing drugs that would specifically block the activity of Arm methyltransferases and thereby re-sensitize pathogenic bacteria to aminoglycoside antibiotics.

Structural basis for the methylation of G1405 in 16S rRNA by aminoglycoside resistance methyltransferase Sgm from an antibiotic producer: a diversity of active sites in m7G methyltransferases.,Husain N, Tkaczuk KL, Tulsidas SR, Kaminska KH, Cubrilo S, Maravic-Vlahovicek G, Bujnicki JM, Sivaraman J Nucleic Acids Res. 2010 Jul 1;38(12):4120-32. Epub 2010 Mar 1. PMID:20194115^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kojic M, Topisirovic L, Vasiljevic B. Cloning and characterization of an aminoglycoside resistance determinant from Micromonospora zionensis. J Bacteriol. 1992 Dec;174(23):7868-72. PMID:1447159
↑ Savic M, Lovric J, Tomic TI, Vasiljevic B, Conn GL. Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics. Nucleic Acids Res. 2009 Sep;37(16):5420-31. doi: 10.1093/nar/gkp575. Epub 2009, Jul 9. PMID:19589804 doi:10.1093/nar/gkp575
↑ Husain N, Tkaczuk KL, Tulsidas SR, Kaminska KH, Cubrilo S, Maravic-Vlahovicek G, Bujnicki JM, Sivaraman J. Structural basis for the methylation of G1405 in 16S rRNA by aminoglycoside resistance methyltransferase Sgm from an antibiotic producer: a diversity of active sites in m7G methyltransferases. Nucleic Acids Res. 2010 Jul 1;38(12):4120-32. Epub 2010 Mar 1. PMID:20194115 doi:10.1093/nar/gkq122