2HDN

Trypsin-modified Elongation Factor Tu in complex with tetracycline at 2.8 Angstrom resolution

Summary for 2HDN

• Entry DOI: 10.2210/pdb2hdn/pdb
• Related: 2HCJ
• Descriptor: Elongation factor EF-Tu, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: trypsin-modified ef-tu, gtpase center, complex with tetracycline, translation
• Biological source: Escherichia coli; More
• Total number of polymer chains: 12
• Total formula weight: 249861.11

Authors

Mui, S.,Heffron, S.E.,Aorora, A.,Abel, K.,Bergmann, E.,Jurnak, F. (deposition date: 2006-06-20, release date: 2006-10-31, Last modification date: 2024-04-03)

Primary citation

Heffron, S.E.,Mui, S.,Aorora, A.,Abel, K.,Bergmann, E.,Jurnak, F.
Molecular complementarity between tetracycline and the GTPase active site of elongation factor Tu.
Acta Crystallogr.,Sect.D, 62:1392-1400, 2006

PubMed Abstract: Two crystal forms of a complex between trypsin-modified elongation factor Tu-MgGDP from Escherichia coli and the antibiotic tetracycline have been solved by X-ray diffraction analysis to resolutions of 2.8 and 2.1 A, respectively. In the P2(1) form, cocrystals were grown from a solution mixture of the protein and tetracycline. Six copies of the trypsin-modified EF-Tu-MgGDP-tetracycline complex are arranged as three sets of dimers in the asymmetric unit. In the second crystal form, tetracycline was diffused into P4(3)2(1)2 crystals, resulting in a monomeric complex in the asymmetric unit. Atomic coordinates have been refined to crystallographic R factors of 18.0% for the P2(1) form and 20.0% for the P4(3)2(1)2 form. In both complexes, tetracycline makes significant interactions with the GTPase active site of EF-Tu. The phenoldiketone moiety of tetracycline interacts directly with the Mg(2+), the alpha-phosphate group of GDP and two amino acids, Thr25 and Asp80, which are conserved in the GX(4)GKS/T and DX(2)G sequence motifs found in all GTPases and many ATPases. The molecular complementarity, previously unrecognized between invariant groups present in all GTPase/ATPases and the active moiety of tetracycline, may have wide-ranging implications for all drugs containing the phenoldiketone moiety as well as for the design of new compounds targeted against a broad range of GTPases or ATPases.

PubMed: 17057344
DOI: 10.1107/S0907444906035426

Experimental method

X-RAY DIFFRACTION (2.8 Å)