2c77: Difference between revisions
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==Overview== | ==Overview== | ||
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 .. | 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. | ||
==About this Structure== | ==About this Structure== | ||
2C77 is a | 2C77 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with MG, GNP, GEA and PEG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dGTPase dGTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.5.1 3.1.5.1] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2C77 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: translation elongation factor]] | [[Category: translation elongation factor]] | ||
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Revision as of 13:38, 5 November 2007
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EF-TU COMPLEXED WITH A GTP ANALOG AND THE ANTIBIOTIC GE2270 A
OverviewOverview
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.
About this StructureAbout this Structure
2C77 is a Single protein structure of sequence from Thermus thermophilus with MG, GNP, GEA and PEG as ligands. Active as dGTPase, with EC number 3.1.5.1 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
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
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