1ha3: Difference between revisions

Aurodox is a member of the family of kirromycin antibiotics, which inhibit, protein biosynthesis by binding to elongation factor Tu (EF-Tu). We have, determined the crystal structure of the 1:1:1 complex of Thermus, thermophilus EF-Tu with GDP and aurodox to 2.0-A resolution. During its, catalytic cycle, EF-Tu adopts two strikingly different conformations, depending on the nucleotide bound: the GDP form and the GTP form. In the, present structure, a GTP complex-like conformation of EF-Tu is observed, although GDP is bound to the nucleotide-binding site. This is consistent, with previous proposals that aurodox fixes EF-Tu on the ribosome by, locking it in its GTP form. Binding of EF-Tu.GDP to aminoacyl-tRNA and, mutually exclusive binding of kirromycin and elongation factor Ts to EF-Tu, can be explained on the basis of the structure. For many previously, observed mutations that provide resistance to kirromycin, it can now be, understood how they prevent interaction with the antibiotic. An unexpected, feature of the structure is the reorientation of the His-85 side chain, toward the nucleotide-binding site. We propose that this residue, stabilizes the transition state of GTP hydrolysis, explaining the, acceleration of the reaction by kirromycin-type antibiotics.

1HA3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_aquaticus Thermus aquaticus] with MG, GDP, MAU and BME 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 Sites: GDA, GDB, MAA, MAB, MGA and MGB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HA3 OCA].  

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