“…The D109K mutation, described in this study, as well as Y112S in S. typhimurium (7,13) conferring EF-G resistance to FA is in -strand neighboring the helix 115-128 in which several FA-resistant mutations found in vivo are clustered (10). None of these mutations is far from the GTP/GDP binding site and may affect the GDP/GTP exchange by interference with conformational changes mentioned above (6,13).…”
Section: Discussionmentioning
confidence: 99%
“…Fusidic Acid-sensitive Mutations-Numerous mutations conferring EF-G resistance to FA have been selected and characterized in vivo (6,13). However, FA-hypersensitive mutants of EF-G were unknown so far.…”
Section: Discussionmentioning
confidence: 99%
“…Many of the numerous FA-resistant mutants are located at interfaces of EF-G domains (6,13). FA molecule is too small to have contacts with all amino acid residues involved in the mutations, because it binds stoichiometrically to the ribosomal complex (24).…”
Section: Discussionmentioning
confidence: 99%
“…Whereas EF-Tu undergoes large conformational changes in its functional cycle (3)(4)(5), only smaller changes have been identified crystallographically for EF-G (6). In EF-G, domains 3-5 can rotate by 10°as a block with regard to the other part of the molecule, i.e.…”
mentioning
confidence: 99%
“…Numerous mutants conferring kirromycin resistance in EF-Tu (8 -9) or FA resistance in EF-G from Salmonella typhimurium (10) and from Staphylococcus aureus (6) were identified and phenotypically characterized in vivo. Based on the tertiary structures of EF-Tu (3, 4,) and EF-G (11)(12), it was suggested that antibiotic-resistant mutations influence conformational dynamics of the factors (8 -9, 13).…”
“…The D109K mutation, described in this study, as well as Y112S in S. typhimurium (7,13) conferring EF-G resistance to FA is in -strand neighboring the helix 115-128 in which several FA-resistant mutations found in vivo are clustered (10). None of these mutations is far from the GTP/GDP binding site and may affect the GDP/GTP exchange by interference with conformational changes mentioned above (6,13).…”
Section: Discussionmentioning
confidence: 99%
“…Fusidic Acid-sensitive Mutations-Numerous mutations conferring EF-G resistance to FA have been selected and characterized in vivo (6,13). However, FA-hypersensitive mutants of EF-G were unknown so far.…”
Section: Discussionmentioning
confidence: 99%
“…Many of the numerous FA-resistant mutants are located at interfaces of EF-G domains (6,13). FA molecule is too small to have contacts with all amino acid residues involved in the mutations, because it binds stoichiometrically to the ribosomal complex (24).…”
Section: Discussionmentioning
confidence: 99%
“…Whereas EF-Tu undergoes large conformational changes in its functional cycle (3)(4)(5), only smaller changes have been identified crystallographically for EF-G (6). In EF-G, domains 3-5 can rotate by 10°as a block with regard to the other part of the molecule, i.e.…”
mentioning
confidence: 99%
“…Numerous mutants conferring kirromycin resistance in EF-Tu (8 -9) or FA resistance in EF-G from Salmonella typhimurium (10) and from Staphylococcus aureus (6) were identified and phenotypically characterized in vivo. Based on the tertiary structures of EF-Tu (3, 4,) and EF-G (11)(12), it was suggested that antibiotic-resistant mutations influence conformational dynamics of the factors (8 -9, 13).…”
The identity, chemistry, biosynthesis, antimicrobial spectra, molecular mode of action, bacterial resistance mechanisms, side effects, and clinical uses of these important chemotherapeutic agents are discussed.
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