2c78 | pdb_00002c78

EF-Tu complexed with a GTP analog and the antibiotic pulvomycin

spinqualitylabelsall models 2c78, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2c78 is a 1 chain structure with sequence from Thet8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GNP, MG, PUL Related: 1ha3 Activity: dGTPase, with EC number 3.1.5.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [EFTU1_THET8] This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.[HAMAP-Rule:MF_00118_B] 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 Pulvomycin inhibits protein synthesis by preventing the formation of the ternary complex between elongation factor Tu (EF-Tu) x GTP and aa-tRNA. In this work, the crystal structure of Thermus thermophilus EF-Tu x pulvomycin in complex with the GTP analogue guanylyl imino diphosphate (GDPNP) at 1.4 A resolution reveals an antibiotic binding site extending from the domain 1-3 interface to domain 2, overlapping the domain 1-2-3 junction. Pulvomycin binding interferes with the binding of the 3'-aminoacyl group, the acceptor stem, and 5' end of tRNA. Only part of pulvomycin overlaps the binding site of GE2270 A, a domain 2-bound antibiotic of a structure unrelated to pulvomycin, which also hinders aa-tRNA binding. The structure of the T. thermophilus EF-Tu x GDPNP x GE2270 A complex at 1.6 A resolution shows that GE2270 A interferes with the binding of the 3'-aminoacyl group and part of the acceptor stem of aa-tRNA but not with the 5' end. Both compounds, pulvomycin more markedly, hinder the correct positioning of domain 1 over domains 2 and 3 that characterizes the active form of EF-Tu, while they affect the domain 1 switch regions that control the EF-Tu x GDP/GTP transitions in different ways. This work reveals how two antibiotics with different structures and binding modes can employ a similar mechanism of action. Structural basis of the action of pulvomycin and GE2270 A on elongation factor Tu.,Parmeggiani A, Krab IM, Okamura S, Nielsen RC, Nyborg J, Nissen P Biochemistry. 2006 Jun 6;45(22):6846-57. PMID:16734421 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Elongation factor 3D structures

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