PDBsum entry 6ift

Transferase

PDB id: 6ift

Contents

Protein chain

292 a.a.

Ligands

SAM

Waters ×194

PDB id:

6ift

Name:

Transferase

Title:

Ksga from bacillus subtilis in complex with sam

Structure:

Ribosomal RNA small subunit methyltransferase a. Chain: a. Synonym: 16s rrna (adenine(1518)-n(6)/adenine(1519)-n(6))- dimethyltransferase,16s rrna dimethyladenosine transferase,16s rrna dimethylase,s-adenosylmethionine-6-n',n'-adenosyl(rrna) dimethyltransferase. Engineered: yes

Source:

Bacillus subtilis (strain 168). Organism_taxid: 224308. Strain: 168. Gene: rsma, ksga, bsu00420. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.90Å R-factor: 0.179 R-free: 0.235

Authors:

R.Bhujbalrao,R.Anand

Key ref:

R.Bhujbalrao and R.Anand (2019). Deciphering Determinants in Ribosomal Methyltransferases That Confer Antimicrobial Resistance. J Am Chem Soc, 141, 1425-1429. PubMed id: 30624914 DOI: 10.1021/jacs.8b10277

Date:

21-Sep-18 Release date: 30-Jan-19

Protein chain

P37468  (RSMA_BACSU) -  Ribosomal RNA small subunit methyltransferase A from Bacillus subtilis (strain 168)

Seq: 292 a.a.

Struc: 292 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.182 - 16S rRNA (adenine(1518)-N(6)/adenine(1519)-N(6))-dimethyltransferase.
• Reaction: adenosine₁₅₁₈/adenosine₁₅₁₉ in 16S rRNA + 4 S-adenosyl-L-methionine = N₆-dimethyladenosine₁₅₁₈/N₆-dimethyladenosine₁₅₁₉ in 16S rRNA + 4 S-adenosyl-L-homocysteine + 4 H⁺

adenosine(1518)/adenosine(1519) in 16S rRNA + 4 × S-adenosyl-L-methionine (Bound ligand (Het Group name = SAM) corresponds exactly) = N(6)-dimethyladenosine(1518)/N(6)-dimethyladenosine(1519) in 16S rRNA + 4 × S-adenosyl-L-homocysteine + 4 × H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/jacs.8b10277

J Am Chem Soc 141:1425-1429 (2019)

PubMed id: 30624914

Deciphering Determinants in Ribosomal Methyltransferases That Confer Antimicrobial Resistance.

R.Bhujbalrao, R.Anand.

ABSTRACT

Post-translational methylation of rRNA at select positions is a prevalent resistance mechanism adopted by pathogens. In this work, KsgA, a housekeeping ribosomal methyltransferase (rMtase) involved in ribosome biogenesis, was exploited as a model system to delineate the specific targeting determinants that impart substrate specificity to rMtases. With a combination of evolutionary and structure-guided approaches, a set of chimeras were created that altered the targeting specificity of KsgA such that it acted similarly to erythromycin-resistant methyltransferases (Erms), rMtases found in multidrug-resistant pathogens. The results revealed that specific loop embellishments on the basic Rossmann fold are key determinants in the selection of the cognate RNA. Moreover, in vivo studies confirmed that chimeric constructs are competent in imparting macrolide resistance. This work explores the factors that govern the emergence of resistance and paves the way for the design of specific inhibitors useful in reversing antibiotic resistance.