Journal: Antimicrobial Agents and Chemotherapy
Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes
Figure Lengend Snippet: Effects of GE2270A and NAI003 on the electrophoretic mobility of EF-Tu and on in vitro translation. (A) Migration on native polyacrylamide gel of E. coli EF-Tu (preincubated with GTP) in the presence of increasing concentrations (from left to right, 0.1, 0.5, 1, 5, 10, 50, and 100 μM) of GE2270A (lanes 2 to 8) or NAI003 (lanes 9 to 15). (B) Electrophoretic mobility difference between EF-Tu–GTP alone (lane 1) and in the presence of 1 μM GE2270A (lane 2) or of 10 μM NAI003 (lane 3). The two arrows indicate the different migrations of EF-Tu in complex with GE2270A or with NAI003. (C) Inhibition by GE2270A (●) or NAI003 (■) in a protein synthesis system based on an E. coli extract programmed with 027-IF2Cp(A) mRNA.
Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).
Techniques: In Vitro, Migration, Inhibition