Structure of a mutant EF-G reveals domain III and possibly the fusidic acid binding site.
The crystal structure of Thermus thermophilus elongation factor G (EF-G) carrying the point mutation His573Ala was determined at a resolution of 2.8 A. The mutant has a more closed structure than that previously reported for wild-type EF-G. This is obtained by a 10 degrees rigid rotation of domains III, IV and V with regard to domains I and II. This rotation results in a displacement of the tip of domain IV by approximately 9 A. The structure of domain III is now fully visible and reveals the double split beta-alpha-beta motif also observed for EF-G domain V and for several ribosomal proteins. A large number of fusidic acid resistant mutations found in domain III have now been possible to locate. Possible locations for the effector loop and a possible binding site for fusidic acid are discussed in relation to some of the fusidic acid resistant mutations.
Laurberg
M
M
Department of Molecular Biophysics, Centre for Chemistry and Chemical Engineering, Lund University, Lund, SE-221 00, Sweden.
Kristensen
O
O
Martemyanov
K
K
Gudkov
A T
AT
Nagaev
I
I
Hughes
D
D
Liljas
A
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004352:Drug Resistance, Microbial; D005672:Fusidic Acid / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020653:Peptide Elongation Factor G / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D016963:Thermus thermophilus / Q000737:chemistry* / Q000235:genetics
D020653:Peptide Elongation Factor G; D006153:Guanosine Diphosphate; D005672:Fusidic Acid